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Chapter 2 - Stem Cells in Nervous System Development and Regenerative Medicine
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What are embryonic stem cells destined to become in the nervous system?
Neurons (nerve cells) and glial cells (supporting cells)
What is the capacity of unspecialized stem cells to become any tissue or organ cell type, including blood cells, muscles, or neurons?
Pluripotent
What can help control the differentiation of cell types in culture dishes?
Inserting genes or changing chemicals
What are the potential benefits of using stem cells in drug development and understanding organism development?
Improving knowledge of organism development, understanding genes and molecular controls of differentiation, and efficient drug development
In cell therapy, what type of stem cells are used to screen drugs to avoid toxic effects on cell types and organs?
Cell lines
What could lost oligodendroglial cells in a rat model of human demyelinating disease be directed to form?
Specific classes of CNS neurons, extend axons, form synapses with target muscle, and replicate in the spinal cord
Efforts have been made to replace inactive pancreatic beta cells in people with type 1 diabetes to restore what?
Normal levels of insulin
What diseases have trials been conducted with adult stem cells for cell therapy?
Parkinson's disease, amyotrophic lateral sclerosis (ALS), macular degeneration, and severe burns
Where are neural stem cells found in the brain?
Subventricular zone, lateral ventricle, and hippocampal dentate gyrus
What is neurogenesis?
The birth of new nerve cells throughout the lifespan
What can neural stem cells differentiate into?
Oligodendroglia and astrocytes
What are induced pluripotent stem cells (iPS cells) created by?
Genetically reprogramming mature cells to develop characteristics of embryonic stem cells
What is one application of induced pluripotent stem cells in drug development and testing?
Studied in patients undergoing heart surgery, injected in blood or in the injured heart to help heart function
What is a challenge of using adult stem cells for therapy compared to embryonic stem cells?
Adult stem cells are more limited in therapeutic potential and harder to isolate from tissues, with a small number of stem cells found in tissue and limited cell division when removed from the body
How does aging affect the amount and quality of stem cells in the body?
Older cells have decreased numbers, damaged DNA, and a shorter lifespan, making them less likely to be immune rejected
What is required for genetic reprogramming to convert mature cells into induced pluripotent stem cells?
Viral vectors to deliver genetic material into the cells
What structures support neurogenesis, the birth of new nerve cells throughout life span?
Lateral ventricle and hippocampal dentate gyrus
What can neurogenesis differentiate into?
Oligodendroglia and astrocytes
Why are nerve cells found in the hippocampus important?
Due to the mechanism of action of antidepressants
What are induced pluripotent stem cells (IPS cells)?
Cells created by genetically reprogramming mature cells to develop characteristics of embryonic stem cells
Where are IPS cells used in drug development and testing?
Some studies performed in patients undergoing heart surgery, inject in blood or in the injured heart to help heart function
Why is it important to match cell donors when using IPS cells?
To prevent rejection by the immune system
What is required for genetic reprogramming of adult cells?
Viral vectors to get genetic material into adult cells
What can retrovirus vectors used for genetic reprogramming potentially produce?
Cancer
What evidence shows reduced proliferation of brain stem cells in schizophrenia, depression, and bipolar disorder?
There is evidence showing reduced proliferation of brain stem cells in these conditions
What do glial cells provide for neurons?
Metabolic support, protection, and insulation
What are the principal functions of neurons?
To transmit information through electrical signaling over long distances
What is the role of sensory neurons?
They are sensitive to environmental stimuli, convert physical stimuli and internal environment into electrical signals, and transmit information to circuits
What are interneurons?
Nerve cells within the brain and spinal cord that integrate information from sensory neurons and form neural circuits responsible for conscious sensations, recognition, memory, decision making, and cognition
What is the role of motor neurons?
To direct biobehavioral responses appropriate for the situation
What are the common features of neurons despite varying in structural arrangements and size according to specific functions?
Transmission of information through electrical signaling over long distances
What are the principal functions of glial cells?
To provide metabolic support, protection, and insulation for neurons
What are the histological methods used for microscopic study of tissues, including brain tissue?
Thin slicing of brain tissue and perfusion with salt solution to remove blood, followed by fixation to kill microorganisms, prevent enzymatic damage, and harden soft tissues
What converts physical stimuli and the internal environment into electrical signals?
Sensory neurons
Where does information from sensory neurons go to?
Circuits, interneurons, nerve cells within the brain and spinal cord
What is responsible for conscious sensations, recognition, memory, decision-making, and cognition?
Neural circuits
What directs the biobehavioral response appropriate for a situation?
Motor neurons
What is the function of the soma (cell body) of a neuron?
Contains the nucleus and organelles to maintain cell metabolic function, synthesis of proteins, enzymes, receptors, and parts of the cell membrane
What is the Golgi technique used for in studying neurons?
To see fine cellular details, then examined with light, micro, or electronic microscopy
What is the function of dendrites in a neuron?
Projections from the soma that receive signals from other neurons
What is the role of transcription factors in protein production?
They direct protein production by modifying the transcription rate
What is the first step in protein production from DNA?
Transcription, where mRNA makes a copy of the active gene
Where does mRNA go after transcription to produce proteins?
It attaches to ribosomes in the cytoplasm for translation
What is the role of genes in protein production?
Genes are small portions of chromosomes that code for protein molecules
What is the purpose of a fixative in histological methods?
To kill microorganisms, stop enzymatic damage, and harden soft tissue for study under a microscope
What is the function of the nucleus in a neuron?
It contains pairs of chromosomes inherited from parents and is the coding region for protein synthesis
What is the function of neurons in the brain and spinal cord?
To transmit information and process sensory stimuli for conscious awareness and motor responses
What are chromosomes made up of?
Chromosomes are made up of long DNA strands that contain genes.
What are genes?
Genes are small portions of the chromosome that code for protein molecules.
What is the function of transcription factors?
Transcription factors are nuclear proteins that direct protein production by modifying the transcription of specific genes.
How can prolonged stress and chronic drug use affect protein production?
Prolonged stress and chronic drug use can turn on or off the production of particular proteins by modifying the activity of transcription factors.
What is the role of CREB in gene expression?
CREB binds to promoter regions of genes and modifies the rate of transcription, influencing protein production.
Describe the process of transcription.
During transcription, messenger RNA (mRNA) is created as a copy of the active gene, and it carries the nucleotide sequence to direct the amino acid sequence of the protein.
What happens during translation?
During translation, proteins are produced using the nucleotide sequence carried by mRNA to direct the amino acid sequence, a process carried out by ribosomes.
What are dendrites and what is their function?
Dendrites are projections from the soma that receive information from other cells. They have receptors that selectively respond to neurochemicals released from other neurons.
How do dendritic spines contribute to the complexity of dendritic trees?
Dendritic spines increase the surface area for receiving signals and contribute to the complexity of synaptic connections with other neurons, influencing brain function.
How do dendritic spines change in response to synaptic transmission?
Dendritic spines constantly modify and change shape in response to changes in synaptic transmission.
Why do individuals with intellectual disabilities often have small and immature dendritic spines?
Individuals with intellectual disabilities may have small and immature dendritic spines due to the failure of maturation into larger spines or the inability to maintain spine structure.
What is the significance of large dendritic spines for retaining knowledge?
Large dendritic spines play a crucial role in retaining knowledge, as the complexity of dendritic spines allows for effective communication between neurons.
How do individuals with schizophrenia differ in dendritic spine characteristics?
Individuals with schizophrenia typically have normal-sized dendritic spines but reduced spine density in the prefrontal cortex.
What is an axon and what is its function?
An axon is a single tubular extension that conducts electrical signals from the cell body to the terminal buttons. It transmits action potentials generated at the axon hillock.
What are axon collaterals and how do they influence neural communication?
Axon collaterals are branches formed when the axon splits. They allow the axon to influence multiple cells and enhance neural communication.
What are dendritic spines and why are they important for retaining knowledge?
Dendritic spines are small protrusions on dendrites that are important for retaining knowledge. Failure of these spines to mature into larger spines or maintain spine structure can lead to intellectual disabilities.
What is the role of axons in synaptic transmission?
Axons are single tubular extensions that conduct electrical signals from the cell body to the terminal buttons. They vary in length and diameter and transmit action potentials generated at the axon hillock.
What is the function of axon collaterals?
Axon collaterals are branches formed when the axon splits at the end of axons terminal buttons. They influence more cells by transmitting signals to multiple neurons.
What is contained in the axon terminals or boutons of neurons?
Axon terminals or boutons contain synaptic vesicles, which are small packets that store neurochemicals. These vesicles provide the capacity for chemical transmission of information across the synapse.
What is the role of synapse in information transmission between nerve cells?
The synapse is the junction between two nerve cells and consists of the presynaptic nerve terminal, synaptic cleft, and postsynaptic cell. It allows for the transmission of incoming signals from one neuron to another.
What is the function of neurons in the body?
Neurons take in oxygen, nutrients, and drugs, secrete metabolic waste products, and generate energy from glucose through mitochondria to produce ATP.
What is the role of myelin in neuronal conduction?
Myelin wraps most axons with a fatty insulating coating, increasing the speed of conduction along the axon. Thicker myelin results in quicker conduction and reduces the energy required to restore the neuron to its resting state after an action potential.
What is multiple sclerosis (MS) and how does it affect the body?
Multiple sclerosis is an autoimmune disease where the immune system attacks the protein in myelin made by oligodendrocytes. This results in myelin loss in the CNS (brain, spinal cord, and optic nerves), causing issues with nerve signal conduction.
What is epigenetics and how can it impact gene expression?
Epigenetics can alter the rate of gene expression by inducing transcription factors, DNA methylation, and chromatin remodeling. DNA methylation involves environmentally induced covalent attachment of methyl groups to genes, typically resulting in decreased gene expression. Chromatin remodeling can increase or decrease gene transcription by changing the structure of chromatin.
Explain the role of synapse in information transmission between nerve cells.
The synapse consists of the presynaptic nerve terminal, synaptic cleft, and postsynaptic cell. It is responsible for the transmission of incoming signals from one nerve cell to another. Convergence refers to neurons receiving and integrating signals from other cells, while divergence involves neurons transmitting integrated signals back out to many neurons.
What is the role of nodes of Ranvier in the conduction of electrical signals along an axon?
Nodes of Ranvier are in the gaps where the myelin is not continuous, allowing for the regeneration of action potentials during the conduction of electrical signals along the axon.
How can epigenetics alter the rate of gene expression?
Epigenetics can alter the rate of gene expression by inducing transcription factors, DNA methylation, and chromatin remodeling.
What is the effect of DNA methylation on gene expression?
DNA methylation involves the environmentally induced epigenetic covalent attachment of methyl groups to genes, usually resulting in a decrease in gene expression.
What is the role of chromatin remodeling in gene transcription?
Chromatin remodeling can either increase or decrease gene transcription by regulating the tightness of chromatin structure through histone proteins.
What are examples of epigenetic mechanisms?
Epigenetic mechanisms include DNA methylation, histone acetylation, histone methylation, and histone phosphorylation.
How can epigenetic mechanisms explain differences in phenotype between monozygotic twins?
Although monozygotic twins have identical genes, epigenetic modifications can lead to differences in gene expression and the development of disorders like schizophrenia, bipolar disorder, cancer, diabetes, etc.
How do drugs of abuse affect gene expression through epigenetic mechanisms?
Drugs of abuse can enhance histone acetylation of multiple genes, leading to persistent changes in gene expression that contribute to drug-seeking behavior and addiction.
What was observed in a study where an enzyme that removes acetyl groups from histones was inhibited?
Inhibiting the enzyme led to reduced drug-seeking behavior in lab animals and a lower probability of relapse when re-exposed to cocaine, indicating the role of histone acetylation in addiction.
How do epigenetic factors contribute to complex disorders like anxiety and depression?
Epigenetic factors can help understand the link between early life events like abuse or neglect and the increased occurrence of clinical depression and anxiety disorders later in life, offering insight beyond genetic factors.
What role does axoplasmic transport play in neurons?
Axoplasmic transport is responsible for transporting proteins along microtubules of the cytoskeleton to various destinations throughout the neuron.
What is the process of anterograde transport in axoplasmic transport?
Anterograde transport moves newly synthesized proteins from the soma to their designated destinations within the neuron.
What can reexposure to cocaine help explain in complex disorders like anxiety and depression?
It may help explain why some disorders appear to run in families and show no classic genetic transmission.
What percentage of risk for developing a disease do genetic polymorphisms identified through sophisticated molecular techniques contribute to?
About 1% of the risk for developing the disease.
What link can be understood between early life events like abuse/neglect and the increased occurrence of clinical depression and anxiety disorders later in life?
It can help to understand the link between early life events and later occurrence of clinical depression and anxiety disorders.
What is axoplasmic transport responsible for?
Transporting proteins along microtubules of the cytoskeleton to various destinations throughout the neuron.
What does anterograde transport in axoplasmic transport do?
It moves newly synthesized proteins from the soma toward the axon terminals.
What does retrograde transport in axoplasmic transport do?
It moves waste products back to the soma from the terminals.
What does axoplasmic transport depend on for its function?
It depends on the structures of the cytoskeleton.
What is the cytoskeleton matrix composed of?
Tubular structures.
chapter 7.pdf Flashcards
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What is the key neurotransmitter in the peripheral nervous system (PNS)?
Acetylcholine (ACh)
How is acetylcholine (ACh) synthesized in the body?
Synthesized by a small number of neurons in the brain using precursors choline and acetyl coenzymes along with choline acetyltransferase (ChAT) to transfer the acetyl group from acetyl CoA to choline.
Where does choline, a precursor for acetylcholine, come from?
Choline comes from fat in the diet and is also produced in the liver.
What controls the rate of acetylcholine (ACh) synthesis in neurons?
The availability of precursors inside the cell and the rate of cell firing control the rate of ACh synthesis. Cholinergic neurons make more ACh when choline and/or acetyl CoA is available and when neurons are stimulated to fire at a higher rate.
What is the role of the vesicular ACh transporter (VAChT) in neurons?
VAChT transports ACh in the vesicle membrane. It is blocked by vesamicol, increasing the level of ACh in the cytoplasm but decreasing vesicular ACh. VAChT does not affect the rate of ACh synthesis.
What are the effects of overactivity of acetylcholine (ACh) in the body?
Muscle pain in the abdomen and chest, tremors, nausea, vomiting, salivation, and copious sweating can occur due to overactivity of ACh.
How does botulism affect neurotransmission?
Botulism inhibits ACh release, leading to muscular paralysis. Clostridium botulinum, the bacteria that causes botulism, produces a potent toxin that interferes with ACh release at terminals and blocks neurotransmission, resulting in muscle weakness and possible paralysis.
What is the role of acetylcholinesterase (AChE) in the body?
AChE breaks down neurotransmitter into choline and acetic acid. There are 3 forms of AChE: soluble G4, membrane-bound G4, and A12.
What is the function of the VAChT vesicular ACh transporter?
Transport ACh in the vesicle membrane
What is vesamicol and how does it affect ACh levels?
Vesamicol blocks the VAChT transporter, increasing the level of ACh in the cytoplasm but decreasing vesicular ACh
What are the symptoms of overactivity of ACh at synapses in the PNS, as seen in Latrodectus mactans envenomation?
Muscle pain in the abs, chest tremors, nausea, vomiting, salivation, and copious sweating
How does botulism affect ACh release and what symptoms does it cause?
Botulism inhibits ACh release, leading to muscular paralysis. Symptoms include muscle weakness and possible paralysis
What is acetylcholinesterase (AChE) and what is its function?
AChE breaks down neurotransmitters into choline and acetic acid. It prevents muscle receptors from becoming desensitized to the neurotransmitter
What are the three forms of AChE and where are they found?
The three forms of AChE are soluble G4, membrane-bound G4, and A12 at the neuromuscular junction (NMJ). They are found in different locations within the body
How do drugs that block AChE affect neurotransmission?
Drugs that block AChE prevent the inactivation of ACh, leading to increased postsynaptic effects of the transmitter
What are some examples of drugs used for dementia that are AChE inhibitors?
Donepezil, Rivastigmine, and Galantamine are synthetic compounds that enter the brain and inhibit AChE activity
What is the function of the AChE inhibitor pyridostigmine and physostigmine?
They are used to reverse AChE inhibitors, binding temporarily to the enzyme protein to inhibit its action
How do organophosphorus compounds like sarin and soman affect AChE activity?
Organophosphorus compounds irreversibly inhibit AChE activity, leading to rapid accumulation of ACh and symptoms such as profuse sweating, salivation, vomiting, and loss of bladder and bowel control
What is the mechanism of drugs used for dementia like Donepezil, Rivastigmine, and Galantamine?
They block AChE to prevent the inactivation of ACh and increase the postsynaptic effects of the transmitter.
What is the role of AChE inhibitors like pyridostigmine and Physostigmine?
They reversibly inhibit AChE activity by binding temporarily to the enzyme protein, inhibiting its action until the drug dissociates and ACh breakdown is restored.
What is the mechanism of action of organophosphorus compounds like Sarin and Soman?
They irreversibly inhibit AChE activity, leading to rapid accumulation of ACh and overstimulation of cholinergic synapses throughout the CNS and PNS.
What are the symptoms of organophosphate poisoning due to AChE inhibition?
Profuse sweating, salivation, vomiting, loss of bladder control, loss of bowel control, convulsions, and ultimately death through asphyxiation due to muscle paralysis.
What is the role of the basal forebrain cholinergic system?
It is the origin of dense cholinergic innervation of the cerebral cortex and is involved in regulating cognitive functions.
What is the function of anticholinergic drugs like Norflex, Cogentin, Artane, Kemadrin, and Biperiden?
They are used for Parkinson's disease to counteract excessive acetylcholine activity and restore balance to the cholinergic system.
Which neurotransmitter is affected by AChE inhibitors and anticholinergic agents?
Acetylcholine (ACh).
What autoimmune disorder is associated with muscle weakness and affects the neuromuscular junction?
Myasthenia gravis.
What is the role of ChAT and AChE in myasthenic syndromes?
Mutations in the genes encoding ChAT or AChE can lead to myasthenic syndromes, affecting the release, breakdown, and activation of acetylcholine.
Where are the preganglionic neurons of the sympathetic and parasympathetic branches located?
They are located within the CNS and send axons to autonomic ganglia.
What results from mutations in the genes that encode either ChAT or AChE?
Myasthenic syndromes
Where are the preganglionic neurons located for both the sympathetic and parasympathetic branches of the autonomic nervous system?
Within the CNS, sending axons to autonomic ganglia
What are some examples of anticholinergic drugs used for Parkinson's disease?
Norflex, Cogentin, Artane, Kemadrin, Biperiden
What is the origin of dense cholinergic innervation of the cerebral cortex?
Basal forebrain cholinergic system (Nucleus basalis, medial septal nucleus, and diagonal band nuclei)
What do AChE inhibitors do in terms of synaptic availability of ACh?
Boost the synaptic availability of ACh
What can anticholinergic agents like atropine and scopolamine produce?
Memory loss
What is the role of ACh in memory encoding of hippocampal-dependent learning?
Important for memory encoding
Which areas give rise to extensive cholinergic projections in the brain?
Cholinergic neurons in the Laterodorsal tegmental (LDTg) and pedunculopontine tegmental (PPTg) nuclei
What is the function of nicotinic acetylcholine receptors (nAChRs) in muscle cells and neurons of the sympathetic and parasympathetic systems?
Mediate fast excitatory responses
What happens when presynaptic nicotinic acetylcholine receptors located within the brain are activated?
Enhances neurotransmitter release from the nerve terminal by depolarizing the terminal
What type of receptors are selective to agonist nicotine?
Nicotinic Acetylcholine Receptors (nAChRs)
Where are highly concentrated nicotine nAChRs located?
On muscle cells at the Neuromuscular Junction (NMJ) and on ganglion neurons in the sympathetic and parasympathetic systems
What type of receptors are nicotine nAChRs and what ions enter the neuron/muscle through them?
Ionotropic receptors; Na+ and Ca2+ ions
What do nicotine nAChRs cause when activated?
Depolarization of the neuron/muscle
What type of responses do nicotine nAChRs mediate in the autonomic system and NMJ?
Fast excitatory responses
Where are nicotine nAChRs located within the brain?
On the presynaptic nerve terminal
What happens when the presynaptic nicotine nAChRs are activated in terms of the receiving cell firing and neurotransmitter (NT) release?
Activation enhances NT release from the nerve terminal by depolarizing the terminal; it does not affect the firing of the receiving cell
How many subunits make up the muscle nicotinic receptor?
Five subunits: 2 alpha, 1 beta, 1 gamma, and either delta or epsilon
Which subunits must be bonded to form neuronal nicotinic receptors for cognitive function?
2 alpha 4 and 3 beta 2; important for cognitive function
Which muscarinic receptors are found at high levels in the neocortex, hippocampus, thalamus, striatum, and basal forebrain?
M1-M5 muscarinic receptors
What are the second messenger systems activated by M1 and M5 muscarinic receptors?
Metabotropic M1-M5 receptors activate phosphoinositide second messenger systems
Where are M2 and M4 muscarinic receptors located, and what effects do they have on nerve terminals?
Located on cholinergic nerve terminals; inhibit cAMP synthesis, stimulate K+ channel opening, and inhibit nerve terminal Ca2+ channel opening
Which muscarinic receptor agonists are classified as parasympathomimetic agents?
Pilocarpine and arecoline
What are the main effects of muscarinic receptor antagonists atropine and scopolamine?
Atropine counteracts effects of poisoning with a cholinergic agonist; Scopolamine causes drowsiness, euphoria, amnesia, fatigue, and dreamless sleep
Where are M2 muscarinic receptors found and what effects do they have?
Found in cardiac muscle; they lead to postsynaptic inhibition
Where are M3 muscarinic receptors found and what effects do they have?
Found in secretory glands and smooth muscle cells; they lead to postsynaptic excitation
Which muscarinic receptor is responsible for dry mouth and where is it found?
M3 muscarinic receptor; found in secretory glands and smooth muscle cells
What are the effects of ionotropic receptors being in a closed state?
No ions can pass through and the receptor is inactive
What are the effects of ionotropic receptors being in an open state?
Ions can pass through, leading to depolarization or other cellular responses
What leads to postsynaptic inhibition in nerve terminals?
Inhibition of nerve terminal Ca2+ channel opening
Where are M1, M3, and M5 receptors located and what second messenger system do they activate?
Located on cholinergic nerve terminals and activate the phosphoinositide second messenger system
Where is the M5 receptor found and what areas of the brain is it present in?
Found in the hippocampus, hypothalamus, and midbrain dopamine (DA) areas
Which receptor is predominantly expressed in midbrain dopaminergic neurons?
M5 receptor
Where are M2 receptors predominantly found and what is their role in cardiac muscle?
Found in cardiac muscle and play a role in cardiac muscle function
What are the effects of M3 receptors activation on secretory glands and smooth muscle cells?
Stimulation of secretory glands and contraction of smooth muscle cells
What are some parasympathomimetic agents that can cause dry mouth?
Pilocarpine and arecoline
What are the antagonists for cholinergic receptors?
Atropine and scopolamine
What does atropine counteract in cases of poisoning with a cholinergic agonist?
The effects of the poisoning
What are the effects of scopolamine on the body?
Drowsiness, euphoria, amnesia, fatigue, and dreamless sleep
Describe the different states of ionotropic receptors: closed, open, and desensitized.
Closed state: not bound to receptor and channel pore is closed. Open state: binds to agonist ACh or nic and pore opens for ions flow. Desensitized state: pore is closed and cannot be opened, even with agonist binding
What is depolarization block in relation to ionotropic receptors?
Loss of the resting potential of the membrane, causing the cell to be unable to be excited until the agonist is removed and the membrane is repolarized
What is the function of succinylcholine?
It is a muscle relaxant that is resistant to breakdown by acetylcholinesterase (AChE)
What is the mechanism of action of mecamylamine (Inversine)?
It blocks nicotinic acetylcholine receptors (nAChRs) centrally and in autonomic ganglia
What is the role of D-tubocurarine and what type of receptors does it antagonize?
It is an antagonist of muscle nAChRs and is the active ingredient of curare, causing paralysis
What are neonicotinoids and what is their relationship to receptors?
They are agonists that are relatively selective for certain receptors
What is the rate of conversion to the desensitized state?
Resensitization capable of responding to an agonist
What happens during Depolarization block?
The resting potential of the membrane is lost and the cell cannot be excited until the agonist is removed and the membrane is repolarized
What is succinylcholine?
Muscle relaxant Resistant to breakdown by AChE
What is mecamylamine (inversine)?
Blocks nAChR receptors centrally and in autonomic ganglia
What is D-tubocurarine?
Antagonist of muscle nAChR The active ingredient of curare Paralytic
What is the effect of D-tubocurarine on cholinergic transmission?
Little effect on cholinergic transmission since nAChRs are selective to muscle and have low penetrance across the BBB
What are neonicotinoids?
Agonists relatively selective
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chapters 4 & 8.pdf Flashcards
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What are behavioral measures important for in behavioral pharmacology?
Understanding the neurochemical basis of behavior and drug-induced changes, developing animal models of psychiatric disorders, and screening newly designed drugs in preclinical pharmaceutical settings.
What are the advantages of animal studies in pharmacology?
Rigorous control, ability to administer drugs, similarity in brains and behavior to humans, and living conditions.
What is correlational studies in behavioral pharmacology?
The connection between two events that appear related but cannot be assumed to be cause and effect.
What is predictive validity in animal studies?
Measures how closely results from animal tests predict clinically useful effects in humans.
What is construct validity in animal studies?
The extent to which animal measurement tools measure human characteristics of interest.
What is a vehicle solution in pharmacology?
Physiological saline or biocompatible solvent used as a negative control in experiments where the drug agent is absent and the effect of behavior is minimal.
What is a positive control in pharmacology?
An experimental control procedure where a well-characterized active treatment is compared to an experimental treatment.
What is predictive validity in animal testing?
Predictive validity measures how closely results from animal tests predict clinically useful effects in humans.
What is construct validity in animal testing?
Construct validity is the extent to which animal measurement tools measure human characteristics of interest.
What is a negative control in animal testing?
A negative control involves using a vehicle solution, such as physiological saline or a biocompatible solvent, where the drug agent is absent from treatment and the effect of behavior is minimal.
What is a positive control in animal testing?
A positive control is an experimental control procedure where a well-characterized active treatment is compared to an experimental treatment.
What are the characteristics of an ideal animal behavioral test?
Well-validated, specific to a class of drug being screened, sensitive to reflect normal therapeutic range doses, show a dose-response relationship, have the same rank order of potency as therapeutic drugs, and exhibit high reliability.
What is the open field test in animal behavior testing?
The open field test involves placing the animal in a prescribed area divided into squares and tracking fecal droppings to observe the amount of time spent along the walls of the chambers instead of exploring open space. It helps measure anxiety-like behavior.
What is operant conditioning in animal behavior testing?
Operant conditioning is a highly sensitive method to evaluate behaviors, learning, and memory. It involves consequences controlling behavior, and animals learn to respond to reinforcement to avoid punishment.
What is an operant chamber in animal behavior testing?
An operant chamber is a controlled environment where animals are subjected to a schedule of reinforcement in operant conditioning experiments.
What measures motor activity and is used to identify drugs that produce sleep, sedation, or motor impairment?
Open field test
What behavior is indicative of anxiety-like behavior in animals during the open field test?
Low activity and high fecal counts
What method is used to evaluate behaviors related to learning and memory by controlling consequences?
Operant conditioning
What is a fixed ratio reinforcement schedule in operant conditioning?
Reinforcement delivered after a fixed number of responses
What does changing the number of times needed to press in a fixed ratio reinforcement schedule indicate?
How hard the subject is willing to work for reinforcement
What is an interval reinforcement schedule in operant conditioning?
Availability of reinforcement after a certain amount of time has elapsed
What is measured in the tail flick test to assess analgesia in animals?
The latency between the onset of the stimulus and the animal removing its tail
What is the hot plate test used for in drug evaluation?
Assessing analgesia based on the latency between an increase
What is the tail flick test used for?
Measuring analgesia by correlating the latency between onset of stimulus and animal removal of the tail with pain intensity
What is the hot plate test used for?
Measuring analgesia by observing latency between an increase in plate temperature and animal response such as licking paws, kicking hind paws, vocalizing, or attempting to escape
What is operant analgesia testing?
Subject learns to turn off foot shock by pressing a lever; used to evaluate effectiveness of analgesic drugs by raising the electric shock threshold
What is aversive threshold in operant analgesia testing?
The lowest shock intensity at which the animal first presses the lever; used for mild analgesics like aspirin
What is the purpose of tests of learning and memory in experimental research?
Objective assessment of learning and memory abilities, but does not determine if altered responses are due to drug-induced changes in attention, motivation, consolidation, retrieval of memory, or other factors
What is the T-maze or multiple T-maze used for in research?
Maze testing where the subject starts at alleys and has to reach the final goal box containing food or a reinforcer; learning is evaluated based on errors made or time taken to reach the goal box
What is the aversive threshold used for?
Mild analgesics like aspirin
What does the T-maze or multiple T-maze test evaluate?
Learning, based on the number of errors made or time taken to reach the goal box
What is the radial arm maze used for?
Evaluating working memory, with multiple ways from the central choice point, each ending with food at the end
What is the Morris water maze used for?
Showing learned spatial location by navigating to an escape platform hidden below the water surface; used for evaluating spatial memory
What is the purpose of the delayed response test?
To test memory, often impaired by damage to the prefrontal cortex in humans
What task involves the subject holding the location of food in working memory to receive a reward?
Match to sample task, where the animal must choose the correct visual stimulus after seeing a sample
What type of memory is often impaired by damage to the prefrontal cortex in humans?
Working memory
What task involves putting food in a box in front of a subject, closing it, and then having the subject reveal where the food is located?
Delayed response test
In the match to sample task, what must the animal do after being shown a sample?
Pick the visual stimulus that is the same
What type of behavior do measures of anxiety-like behavior typically assess in animals?
Fearfulness or anxiety levels
What is the purpose of the light-dark crossing task in measuring anxiety-like behavior in animals?
To measure the number of crossings between bright and dark sides, time spent on each side, and total motor activity
What do anxiety-reducing drugs typically do to activity levels and time spent in the light side in the light-dark crossing task?
Lower activity and increase time spent in the light side
What is the main objective of the open field test in assessing anxiety levels in animals?
To observe the animal's exploration behavior in a test chamber
Which maze consists of a cross-shaped structure raised off the floor and is commonly used to measure anxiety levels in animals?
Elevated plus maze
What does an increase in open arm exploration in the elevated plus maze indicate regarding anxiety levels in animals?
Reduced anxiety levels or anti-anxiety effect
What is the purpose of the open field test?
To measure anxiety levels in animals by observing their exploration behavior in a lit test chamber.
How do anxiety-reducing drugs affect motor activity in animals?
Anxiety-reducing drugs lower motor activity in animals.
What does the elevated plus maze consist of and how does it measure anxiety levels in animals?
The elevated plus maze is a cross-shaped maze raised off the floor that measures anxiety levels by observing increases in open arm exploration with anxiolytic drugs and reductions after caffeine or amphetamine, which increase anxiety.
What is the purpose of the zero maze in measuring anxiety levels in animals?
The zero maze is a donut-shaped elevated platform with two enclosed and two open sections used to measure anxiety levels in animals based on their behavior in different sections.
What is the significance of the social interaction test in measuring anxiety levels in animals?
The social interaction test involves observing behaviors like sniffing, walking, crawling, and grooming in animals to measure anxiety levels. Reduced social interaction in an unfamiliar test chamber indicates increased anxiety.
What is the novelty-suppressed feeding paradigm used for in animal behavior studies?
The novelty-suppressed feeding paradigm involves presenting food in a potentially threatening environment to observe how long it takes for animals to start eating, indicating anxiety levels.
How are ultrasonic vocalizations used to measure anxiety-like behaviors in young animals?
Ultrasonic vocalizations are recorded in young animals when they are separated from their mother. The frequency and type of vocalizations reflect their anxiety levels.
What does the water lick suppression test, or Vogel test, measure in animal behavior studies?
The water lick suppression test measures anxiety levels by observing changes in water consumption in response to anxiety-reducing drugs. It is insensitive to newer anxiolytics.
What are the defensive burying and marble burying tasks used for in measuring anxiety levels in animals?
Defensive burying tasks involve animals burying an electrified probe in the cage when it causes a shock, indicating anxiety. Marble burying tasks involve burying marbles as a repetitive, anxiety-related behavior.
What paradigm is used to test novelty-suppressed feeding?
Novelty-suppressed feeding paradigm
What test involves prolonging the latency to start eating by presenting food in a potentially threatening environment?
Novelty-suppressed feeding paradigm
What are recorded as signs of anxiety-like behaviors in young animals when separated from their mother?
Ultrasonic vocalizations
What test measures anxiety by recording ultrasonic vocalizations in young animals?
Ultrasonic vocalizations
What test involves presenting water to animals and assessing the suppression of licking behavior as a measure of anxiety?
Water lick suppression test
What test, also known as the Vogel test, screens anxiety-reducing drugs and requires minimal training of animals?
Conflict procedure
What class of drugs is known to increase water consumption in the water lick suppression test?
Benzodiazepines
What task involves inserting an electrified probe in the side of a cage to induce defensive burying behavior in animals?
Defensive burying task
With the use of anxiolytics, what happens to the time spent burying in the defensive burying task?
Decreases
What task involves the burying of marbles by animals as a measure of anxiety-like behavior?
Marble burying task
What type of behavior does the marble burying task model?
OCD (Obsessive-Compulsive Disorder)
What test measures fear by presenting a signal followed by an unavoidable shock to create a conditioned fear association?
Conditioned emotional response
What response is observed when a warning signal is presented during ongoing behavior, leading to behavior suppression and freezing?
Fear-potentiated startle
What measures are used to assess depressivelike behavior in animals?
Reduction in psychomotor activity, neuroendocrine responses, cognitive changes, or changes in eating, sleeping, and deriving pleasure from everyday activities
What test involves forcing rats or mice to swim in a cylinder without any escape, leading to immobility after unsuccessful attempts?
Forced swim test (Behavioral despair)
In the tail suspension test, animals are suspended by the tail from a lever, and what is recorded?
Duration of movements
What concept is demonstrated when animals experience an aversive event and become unable to respond appropriately in subsequent situations?
Learned helplessness
What is suppressed freezing?
Suppressed freezing occurs when the startle response is potentiated by fear.
Describe the basic startle response.
The basic startle response is a measurement of depressivelike behavior in animals.
What is the forced swim test used for?
The forced swim test is used to assess behavioral despair in rats and mice.
How is the tail suspension test conducted?
In the tail suspension test, animals are suspended by the tail from a lever, and the duration of their movements is recorded.
What is learned helplessness?
Learned helplessness occurs when animals experience aversive events and are unable to respond appropriately.
What is chronic mild unpredictable stress?
Chronic mild unpredictable stress involves a series of physically stressful events, leading to depressivelike behaviors, cognitive impairments, increased anxiety-like behaviors, social withdrawal, and reduced preference for sucrose.
What is the impact of chronic defeat stress on animals?
Chronic defeat stress in the resident-intruder paradigm leads to a reduction in motor activity, exploration, sucrose preference, copulatory behaviors, social withdrawal, and metabolic syndrome.
What is maternal separation stress?
Maternal separation stress is induced by separating young animals from their mothers daily in the first few weeks of life, leading to long-term behavioral and neuroendocrine abnormalities in adult animals.
What are some effects of placing a cage next to a cage with an animal inside?
Reduction in motor activity, exploration, sucrose preference, copulatory behaviors, social withdrawal, and metabolic syndrome.
What is needed to reverse the behaviors induced by chronic stress in animals?
Chronic antidepressant administration.
What is maternal separation in animals?
Stress induced by separating young animals from their mothers daily during the first few weeks of life.
What can be evaluated in animal adults due to early stress during maternal separation?
Long-term behavioral and neuroendocrine abnormalities.
chapters 4 & 8.pdf Flashcards
Study
What is the Sucrose preference test used to measure?
Anhedonia
What do animals show a strong preference for in the Sucrose preference test?
Sweetened solution
What is an accurate indicator of abuse potential in humans according to chronic antidepressant treatment?
Self-administration method
What do animals readily self-administer to indicate abuse potential in humans?
Morphine, cocaine, and amphetamine
What is the most valid model of drug seeking in humans according to chronic antidepressant treatment?
Breakpoint
What does the Breakpoint measure in drug seeking behavior?
The effort required exceeds the reinforcing value
What brain circuits are needed for reinforcement of behavior according to chronic antidepressant treatment?
Electrical self-stimulation
What do animals work to stimulate in brain circuits needed for reinforcement of behavior?
Clusters of neurons
What do morphine and heroin increase in response to low levels of electrical stimulation according to chronic antidepressant treatment?
Brain reinforcement mechanism
What is conditioned place preference based on?
Classically conditioned association between drug effect and environment
In conditioned place preference, where does the animal spend more time if the drug is rewarding?
In the compartment associated with the rewarding drug
What are drugs as discriminative stimuli used for in operant tasks?
To signal reinforcement for a subject
What do automated quantification of behavior tools provide in psychopharmacological research?
Computer version evolving technology used to discern a wide array of behaviors
What is the goal of translational research in psychopharmacology?
To transform discoveries from basic neuroscience research into clinical applications for treating mental and neurological disorders
What does a Stop signal task measure in behavioral research?
Impulsivity
What is the process by which a drug is rewarding if the animal spends more time in that compartment compared to the aversive drug?
Conditioned place preference
What is the term for a stimulus that signals reinforcement for a subject in an operant task?
Discriminative stimulus
What type of research involves transforming discoveries from basic neuroscience research into clinical applications for treating mental and neurological disorders?
Translational research
What is the procedure used to measure impulsivity that involves the failure of cortical control mechanisms to suppress inappropriate responses?
Stop signal task
What technique in neuroscience allows researchers to implant a device into the brain of an anesthetized animal with precision, often used for lesioning and microinjection studies?
Stereotaxic surgery
What type of lesions are created by applying heat to the cells near the tip of an insulated electrode?
Electrolytic lesions
How are specific neurotoxins injected to identify the brain area responsible for drug-induced changes in behavior?
Directly into the brain
What device is used to identify lesions in the brain through MRI or CT scans?
Lesioning and microinjection Stereotaxic device
What is used to insulate the electrode and provide stops at the tip?
Insulated electrode
How do electrolytic lesions destroy tissue in the brain?
By destroying cell bodies, dendrites, and axons near the tip of the electrode
What is a neurotoxin and how is it used in neuroscience research?
A chemical that damages nerve cells, injected via cannula to destroy cells; used to identify brain areas responsible for drug-induced changes in behavior
What method is used to measure neurotransmitter release in the brain during active behavior?
Microdialysis
What is the purpose of artificial CSF being pumped through a microdialysis cannula during microdialysis?
To sample material in the extracellular space at precise sites
What technique separates a sample into parts to determine the concentration of molecules of interest during microdialysis?
HPLC (High-Performance Liquid Chromatography)
What does invivo voltammetry measure in freely moving animals?
Neurochemicals in the extracellular fluid
How do changes in the flow of current reflect changes in the concentration of electroactive substances in invivo voltammetry?
Through small electrical potentials through microelectrodes
What is the purpose of using macroelectrodes in electrophysiological stimulation and recording?
To activate cells at the tip and record the electrical response of neurons in the brain
What is the main function of microelectrodes in neuroscience research?
To enable intracellular recording of single cells or record extracellular fluid near single cells
What technique is used to determine the concentration of molecules of interest invivo?
Voltammetry
What does invivo voltammetry measure in freely moving animals?
Neurochemicals in the extracellular fluid
What reflects changes in the concentration of electroactive substances when a small electrical potential goes through microelectrodes?
Changes in the flow of current
How can researchers evaluate neurotransmitter release in real-time using electrophysiological stimulation and recording?
By implanting macroelectrodes that can activate cells and record the summated electrical response of neurons in the brain
Where are microelectrodes implanted for intracellular recording of a single cell or extracellular fluid near a single cell?
Into the brain tissue or around the cell of interest
What type of recording involves an anesthetized animal and records the response of individual cells under monitored conditions?
Intracellular recording
What type of recording can be done on mobile animals and only records the occurrence of action potentials in nearby neurons?
Extracellular recording
What technique is used to study the individual function of ion channels by attaching a micropipette to the cell membrane and observing channel opening and closing in real-time?
Patch clamp electrophysiology
How is a part of the cell membrane attached to the micropipette during patch clamp electrophysiology?
By suction
What is used in neurochemical analysis assays to measure the number of receptors in a brain area and is conducted using a radioligand binding assay in homogenate tissue?
Homogenates
What technique is used to locate specific receptors in the brain by incubating a ligand that is radioactively labeled under optimal binding conditions with ground-up tissue?
Autoradiography
In radioligand binding, if radioligands are not bound, what is the implication?
The receptors being studied may not have a high affinity to the drugs used or may not be present in the region studied
What is the purpose of using autoradiography in neurochemical analyses?
To locate certain receptors in the brain.
What is the process of radioligand binding assay in homogenate tissue?
Homogenates are used to measure the number of receptors in a brain area by incubating radioactively labeled ligands under optimized conditions to assess binding.
What does specificity refer to in radioligand binding assays?
The ligand should only bind to the specific receptor of interest in the tissue, and nonradioactive competing ligands can displace radioactive binding to show specificity.
What is saturability in the context of receptor binding studies?
It refers to the finite number of receptors in a given amount of tissue, where increasing the radioligand binding saturates all available receptor sites.
What is the significance of receptor autoradiography in neurochemical analysis?
It provides information on receptor number and affinity for a drug in specific parts of brain tissue, allowing visualization of receptor distribution.
What is the purpose of adding a high concentration of nonradioactive competing ligands in tissue experiments?
To show that radioactive binding is displaced by the competition of nonradioactive ligands.
How are nonspecific sites handled in data calculated for specific binding in tissue experiments?
They are subtracted from the data to get accurate measurements of specific binding.
What does saturability refer to in tissue experiments with receptors?
The finite number of receptors in a given amount of tissue.
What happens when the amount of radioligand is increased in tissue binding experiments?
Binding increases until all receptor sites are filled.
What does Bmax represent in receptor binding studies?
The maximum binding capacity of receptors in a tissue sample.
What does Kd (dissociation constant) estimate in receptor binding studies?
The receptor affinity for a ligand.
Why must unbinding in receptor binding studies be consistent with the reversal of physiological effects of the ligand?
To ensure that the measured binding is relevant to the biological function of the ligand.
What information does receptor autoradiography provide in research studies?
It tells the receptor number and affinity for a drug in a specific part of the brain tissue.
How is receptor autoradiography conducted in studies to visualize receptors within the brain?
By using radioligand binding on slide-mounted tissue slices, washing away unbound radioactive drugs, and processing the slices with autoradiography.
What is the purpose of in vivo receptor binding studies conducted with autoradiographic processing on animals injected with radiolabeled drugs?
To show where a particular drug or neurotransmitter binds in an intact animal.
What is the role of enzyme activity assays in biological research?
To measure the speed and efficiency of enzymatic reactions in biological systems.
How are antibodies used in research to identify and measure receptors and proteins?
Antibodies are proteins produced to recognize and bind to specific antigens, allowing for the detection and measurement of target proteins.
What is autoradiography used for in animal studies?
It shows where a particular drug or neurotransmitter binds in an intact animal.
What is the purpose of assays of enzyme activity in research studies?
Enzymes are proteins that act as biological catalysts to speed up reaction rates without being used up in the process.
How is antibody production used to identify receptors and proteins in research studies?
Antibodies are produced by white blood cells of the immune system to recognize, attack, and destroy foreign substances. They are created by injecting antigens into a host animal and collecting antibody from blood samples.
What is immunocytochemistry (ICC) used for in tissue analysis?
It involves incubating tissue slices with antibodies to visualize antigen-containing cells. This method is useful for identifying peptides in tissues.
How is Western blotting different from immunocytochemistry (ICC)?
Western blotting detects specific proteins in tissues instead of tissue slices. It involves gel electrophoresis to separate homogenates and uses antibodies for detection.
What is the principle behind radioimmunoassay (RIA) in research studies?
RIA involves the competitive binding of antibodies to their antigens, making procedures highly specific and sensitive for molecules of interest.
How does ELISA (enzyme-linked immunosorbent assay) work in identifying antigens in samples?
ELISA uses an enzyme that acts on the antigen-antibody complex to produce a detectable signal, enabling the quantification of antigens in samples.
What is the purpose of antibodies in Western blot?
Antibodies detect specific proteins in tissue slices
How does gel electrophoresis work in separating homogenate?
Gel electrophoresis separates homogenate out
What is the step after applying the first antibody in Western blot?
Rinse to remove unbound antibody
What is the purpose of the second antibody in Western blot?
To bind to the first antibody and create a chemical reaction to visualize it
What is the principle of radioimmunoassay (RIA)?
It involves competitive binding of antibody to its antigen
How do antibodies contribute to the specificity and sensitivity of procedures in protein detection?
Antibodies make procedures highly specific for molecules of interest and very sensitive
What does ELISA stand for and what is its function?
ELISA stands for Enzyme-Linked Immunosorbent Assay, it is used to quantify antigens in a sample
How does a microplate reader measure the product in an ELISA assay?
The microplate reader measures the color change which is proportional to the amount of substance in the sample
What is the purpose of in situ hybridization?
To locate cells in tissue slices that are manufacturing specific proteins or peptides
How are probes created for in situ hybridization?
Probes are created by labeling single-stranded fragments of RNA with sequences complementary to mRNA of interest
What technique is used to measure the amount of mRNA and not visualize its location?
Northern blot and dot blot are used for measuring mRNA amount, not visualization
What is the purpose of DNA microarrays (DNA chips/gene chips) in gene expression analysis?
DNA microarrays are used to measure gene expression levels
What is one method used to detect specific mRNA molecules responsible for protein synthesis in neurons?
Creating probes by labeling single-stranded fragments of RNA with complementary base pair sequences to mRNA of interest.
What is the purpose of using radioactively or dye-labeled probes in mRNA detection?
To allow the probes to attach to tissue samples for visualization.
What methods can be used for mRNA detection in tissues, including homogenates, northern blot, and dot blot?
Manufacturing probes, attaching them to tissue samples, washing and dehydrating the tissue, then exposing it to X-ray film.
What is the function of DNA microarrays or gene chips in molecular biology research?
To measure the expression levels of thousands of genes simultaneously.
What is the significance of GWAS (Genome-Wide Association Studies) in genetics research?
They use gene chips to study the association between large sets of single nucleotide polymorphisms (SNPs) and traits or diseases.
What do copy number variants (CNVs) refer to in genetics and genomics?
Chromosomal abnormalities where parts of chromosomes are duplicated, deleted, inverted, or translocated.
How does RNA sequencing contribute to molecular biology research?
It allows researchers to assess the expression levels of thousands of genes and measure the cellular transcriptome and protein expression.
What does pharmacogenetics focus on in terms of drug responses?
Using genetic factors to predict individual responses to therapeutic or adverse effects of drugs.
How does autoradiography of dynamic cell processes contribute to neuroscience research?
It allows for tracing active processes in the brain, such as blood flow, oxygen consumption, glucose utilization, and cerebral protein synthesis rates that indicate neural activity.
What is the role of 2-deoxyglucose autoradiography in studying nerve cell firing and metabolic rates?
It is used to measure the increase in nerve cell firing and metabolic rate during active processes.
What does transcriptomics measure?
Cellular transcriptome, actual protein expression at a given time.
What is the purpose of sequencing entire transcriptome unbiased?
To detect novel transcripts.
What is pharmacogenetics?
Knowledge of genetic factors that can predict therapeutic or adverse responses to drug effects.
What does autoradiography of dynamic cell processes involve?
Tracing active processes in the brain: blood flow, oxygen consumption, local glucose utilization, local rates of cerebral protein synthesis that indicate neural activity.
What is 2DG autoradiography used for?
It increases nerve cell firing and metabolic rate.
chapters 4 & 8.pdf Flashcards
Study
What imaging technique increases resolution and provides a 3D image of the brain by placing the head in a cylindrical x-ray tube?
Computerized tomography (CT)
What imaging technique refines the view of the living brain by using a magnetic field and radiofrequency waves to activate distinct waves emitted by different atoms?
Magnetic resonance imaging (MRI)
What imaging technique complements MRI by evaluating metabolic changes in conditions like Alzheimer's, Parkinson's, depression, and epilepsy, measuring levels of specific molecules and neurotransmitter metabolites?
Magnetic resonance spectroscopy (MRS)
What imaging technique modifies MRI to show the 3D movement of water in neural tissue, providing a structural view of connectivity among brain structures and axonal pathways?
Diffusion tensor imaging (DTI)
What imaging technique localizes radioactively labeled materials injected into living humans, maps their distribution, and tracks gamma photons to locate their origin?
Positron emission tomography (PET)
What imaging technique is similar to PET imaging but is less expensive, easier, and has lower resolution, allowing visualization of brain activity reflected by glucose usage, oxygen usage, and blood flow?
Single photon emission computerized tomography (SPECT)
What imaging technique detects increases in blood oxygenation caused by cell firing, providing anatomical and functional information?
Functional magnetic resonance imaging (fMRI)
What is used to map the distribution of the brain but does not create images of the brain?
Isotopes that decay fast
What can be administered to visualize brain activity and reflect glucose usage, oxygen usage, and blood flow?
Radioactively labeled drugs or ligands
What technique allows for mapping brain areas with increased glucose and blood flow by tracking gamma photons?
Single Photon Emission Computerized Tomography (SPECT)
What does fMRI detect increases in, caused by cell firing?
Blood oxygenation
What does BOLD imaging provide in fMRI?
Anatomical and functional information along with a detailed image
What does resting-state fMRI (rsfMRI) monitor in the brain when an individual is awake but not actively doing a task requiring attention?
Connectivity among brain regions
What network includes the posterior cingulate cortex, medial PFC, ventral anterior cingulate cortex, and parts of the parietal cortex?
Default Mode Network
What does pharmacological MRI (phMRI) analyze in drug development?
Change in brain function after drug administration and shows the location of drug action in the CNS
What is EEG (Electroencephalography) used for in brain activity monitoring?
Detect electrical events in real time
What is qEEG (Quantitative EEG) used for in brain analysis?
Computerized analysis to evaluate large complex data collected in an EEG
What does ERP (Event-Related Potentials) visualize?
Processing of cognitive events
What is phMRI and how is it related to fMRI?
phMRI is a spin-off of fMRI and analyzes changes in brain function after drug administration, showing the location of drug action in the central nervous system (CNS).
What is qEEG and how is it used in personalized medicine?
qEEG, or quantitative EEG, is a computerized analysis technique that evaluates large complex data collected in an EEG, converted into color maps. It helps predict response to treatments and enhances personalized medicine.
What are ERPs in the context of EEG?
ERPs, or event-related potentials, visualize the processing of cognitive responses to a given stimulus as they occur, based on small and raw EEG responses.
What is the CRISPR-Cas9 system used for in genetic engineering?
CRISPR-Cas9 is used to modify genomic sequences by cutting out specified sections of DNA and inserting new DNA. It can examine epigenetic modifications of gene expression and control gene expression using activating proteins.
What is somatic genetic engineering?
Somatic genetic engineering affects the somatic cells of treated individuals, making targeted genetic modifications in non-reproductive cells.
What is CRISPR?
Clustered Regularly Interspaced Short Palindromic Repeats, a technology used for genetic editing
What is the role of guide RNA in CRISPR?
It identifies the genomic sequences to be modified by the Cas9 nuclease
How does CRISPR work in gene editing?
Cas9 nuclease cuts out specified sections of DNA and new DNA is inserted, altering gene expression
What is somatic genetic engineering?
It affects somatic cells of treated individuals, not passed on to offspring
What is human germline engineering?
It edits and modifies the genome in gametes, affecting future generations
What are Knockin mice?
Mice with an inserted gene that is slightly different from the wildtype, producing a modified protein
What are Transgenic mice used for?
To study genetic disorders and ascertain the functional role of modified genes
What is beam walking used for in research studies?
It resembles a human balance beam and helps study motor coordination and balance in rodents
What is Rotarod and its purpose in research?
A horizontally oriented cylinder that rotates at set speeds, used to test motor coordination and balance in rodents
How is swimming performance used in research studies?
It studies the gait pattern during locomotion over a solid surface, providing insights into motor function
What is Prepulse Inhibition of Startle used to study?
It assesses the ability of an individual to inhibit startle responses by applying a weak pre-stimulus before a stronger stimulus
What deficits in schizophrenia are studied in research involving rodent models?
Motor deficits, cognitive impairment, and sensory processing abnormalities
What is cloning and how is it used in research?
It is the cell division process that produces large numbers of identically altered cells, used in genetic engineering and biotechnology
What is optogenetics and its application in research?
It uses light to control the activity of genetically specific cells with high temporal and spatial precision
How is neuronal firing controlled in optogenetics?
Through light-activated channels like ChR2 (Channelrhodopsin2) that depolarize and activate neurons
What is the raised beam used in a study called Beam walking similar to?
It resembles a human gymnastic balance beam
What is a Rotarod?
It is a horizontally oriented cylinder that mechanically rotates at set speeds
What is the study of gait pattern of limb movement during locomotion over a solid surface known as?
Swimming performance
What is Prepulse inhibition of startle study about?
It is the ability of an individual to be studied by applying a weak prepulse stimulus shortly before a startle-inducing stimulus
What are deficits commonly observed in schizophrenia?
Deficits in cloning cell division process that produces large numbers of identically altered cells
What is the process of using light to exert precise control over genetically specific cells called?
Optogenetics
How does ChR2 (Channelrhodopsin2) stimulate cell firing?
It opens a light-activated channel causing depolarization of the cell membrane and cell firing due to Na influx
What is the function of iC1C2 in neuronal firing control?
It forms an inhibitory chloride channel
How does NpHR control neuronal firing?
It acts as a Cl pump with slower onset action
What is Chemogenomics and how is it related to DREADDS?
Chemogenomics is the use of Designer Receptor Exclusively Activated by a Designer Drug (DREADDS) for less invasive and altered g protein binding to control neuronal actions
Where is the synthesis of molecules of dopamine (DA), acetylcholine (ACh), or serotonin (5HT) usually done for neurotransmission?
It is done within the cells that use these transmitters like neurons and glial cells
What type of neurotransmitter is glutamate and what type of neurons predominantly release it?
Glutamate is a fast excitatory neurotransmitter predominantly released by glutamatergic neurons with higher concentrations compared to other cells
How are molecules of glutamate derived for neurotransmission?
They are derived from the normal metabolic breakdown of glucose, with glutamine serving as a precursor which is converted to glutamate with the enzyme glutaminase
How is glutamate packaged and released for neurotransmission?
It is packaged and released from synaptic vesicles using vesicular glutamate transporters such as VGLUT1, VGLUT2, and VGLUT3
What are the cells that use transmitters such as DA, ACh, or 5HT for neurotransmission?
Neurons and glial cells
What is the precursor of glutamate in the synthesis process?
Glutamine
What enzyme is responsible for converting glutamine into glutamate?
Glutaminase
What are the three types of vesicular glutamate transporters responsible for packaging and releasing glutamate?
VGLUT1, VGLUT2, VGLUT3
Where is VGLUT1 primarily found and what function does it serve in neurotransmission?
Mostly in the cortex and hippocampus; sustains firing and vesicle refilling
In what structures is VGLUT2 predominantly located?
Subcortical structures
What happens if there is no VGLUT2 present in the inner hair of the cochlea?
Instant death
What are the consequences of the absence of VGLUT1 and VGLUT3 respectively?
Slow death (VGLUT1) and deafness (VGLUT3)
How is glutamate removed from the extracellular space after release and where does this process primarily occur?
Removed by glutamate transporters on cell membranes, primarily in astrocytes of the brain
What role do EAAT1, EAAT2, and EAAT5 play in the uptake of glutamate after release?
They are glutamate transporters on cell membranes
Why is prolonged high levels of glutamate in the extracellular fluid dangerous?
It can produce excessive neuronal excitation, leading to cell death
Where is EAAT1 primarily transported in the brain for glutamate uptake?
Astrocytes of the cerebellum
What is the role of VGLUT3 in the inner hair cells of the cochlea?
VGLUT3 is responsible for glutamate uptake and release in the inner hair cells of the cochlea.
What happens if there is no VGLUT2 present?
Instant death occurs in the absence of VGLUT2.
What is the consequence of the absence of VGLUT1?
Slow death occurs in the absence of VGLUT1.
What is the outcome of lacking VGLUT3?
Deafness is the result of lacking VGLUT3.
How is glutamate removed from the extracellular space after release?
Glutamate is removed by glutamate transporters on cell membranes.
What are the differences between plasma membrane transporters and EAAT1, EAAT5, and EAAT2?
EAAT1, EAAT5, and EAAT2 are different from plasma membrane transporters and play an important role in taking up glutamate after release.
In which cells are EAATs transported in the brain?
EAATs are transported in astrocytes of the brain.
What are the consequences of prolonged high levels of glutamate in the extracellular fluid?
Prolonged high levels of glutamate can lead to excessive neuronal excitation and cell death.
What is the function of glutamine synthetase in the glutamate-glutamine cycle?
Glutamine synthetase converts glutamate to glutamine in the glutamate-glutamine cycle.
What are the effects of inactivation of glutamate?
Inactivation of glutamate helps in metabolism and removal of ammonia; lack of this can cause brain deformities, seizures, and shorten the lifespan.
What is the role of glutamate as a neurotransmitter in the cerebral cortex?
Glutamate is the main neurotransmitter in the cerebral cortex, used by pyramidal neurons for synaptic plasticity, learning, memory, and cell death in some neurological disorders.
What is the enzyme involved in the metabolism and removal of ammonia?
Glutaminase
What happens when glutamate is inactivated?
Helps in metabolism and removal of ammonia
What are the consequences of the lack of glutaminase?
Brain deformities, seizures, and a short life span
Which neurotransmitter is the main one in the cerebral cortex?
Glutamate
Which type of neurons in the cortex use glutamate?
Pyramidal neurons
Where do the pyramidal neurons project to from the cortex?
Striatum, thalamus, limbic system structures, and brainstem
What functions are associated with glutamate in the cerebral cortex?
Synaptic plasticity, learning, memory, and cell death in some neurological disorders
How many subunits make up ionotropic glutamate receptors?
4 subunits
What is the main response induced by ionotropic glutamate receptors?
Excitatory response
Which ions flow into the postsynaptic cell through AMPA receptors and kainate receptors?
Sodium (Na)
What is the selective agonist for AMPA receptors?
Synthetic amino acid
What subunits make up most excitatory responses to glutamate through AMPA receptors?
2GluA2, 2GluA1, or 2GluA3, and 2GluA4
Which receptors are involved in locomotor activity, coordination, and brain excitability?
Kainate receptors
What subunits make up kainate receptors?
GluK1, GluK2, and/or GluK3
Which ions does the NMDA receptor conduct through its channel?
Sodium (Na) and Calcium (Ca2)
What are the subunits of a kainate receptor?
GluK1, GluK2, GluK3
What ions does the NMDA receptor channel conduct?
Na and Ca2
chapters 4 & 8.pdf Flashcards
Study
What are the two NTS required to stimulate the NMDA receptor and open the ion channel?
Glutamate and glycine
Which receptor sticks out into the extracellular space?
NMDA receptor
What binds to and activates the glycine binding site on the NMDA receptor?
D-serine
What blocks the NMDA receptor channel when resting and opens when the membrane is depolarized?
Mg2
What type of agonist is memantine in relation to the NMDA receptor?
Uncompetitive agonist
Which antagonist can block both AMPA and kainate receptors?
NBQX
What is the function of mGluR1 and mGluR5 in the mGluR group 1?
Mediate excitatory responses by activating phosphoinositide second messenger systems
Where are mGluR2 and mGluR3 located in the mGluR group 2?
Presynaptic
What is the function of Group 3 mGluR4, mGluR6, mGluR7, and mGluR8 in the metabotropic receptor system?
Signal by inhibiting cyclic adenosine monophosphate (cAMP) formation
What is the mechanism of action of antagonist NBQX?
Antagonist NBQX can block both AMPA and kainate receptors, with no effect on NMDA receptors. It reduces locomotor activity and provides protection against electrically and chemically induced seizures.
How are metabotropic receptors classified based on second messenger systems?
Metabotropic receptors are divided into 3 groups based on their second messenger systems. Group 1 includes mGluR1 and mGluR5, which mediate excitatory responses by activating phosphoinositide second messenger systems and are located on the postsynaptic side. Group 2 consists of mGluR2 and mGluR3, which are presynaptic. Group 3 includes mGluR4, mGluR6, mGluR7, and mGluR8, signaling by inhibiting cyclic adenosine monophosphate (cAMP) formation.
What is Fragile X syndrome (FXS) and its underlying cause?
Fragile X syndrome (FXS) is a congenital disorder that results in inherited intellectual disability and autistic symptoms. It is caused by mutations in the FMR1 gene, which codes for the FMRP protein. FMRP functions in long-term depression (LTD) in the hippocampus.
What is the role of mGluR1 and mGluR5 in Fragile X syndrome?
In Fragile X syndrome, the loss of FMRP leads to exaggerated functions of mGluR1 and mGluR5. These receptors play a role in long-term potentiation (LTP), contributing to the weakening of neurotransmission at affected synapses.
What is the function of mavoglurant?
Mavoglurant is a selective mGluR5 antagonist that targets NMDA receptors in learning and memory processes. It can lead to the strengthening of synapses through long-term potentiation (LTP).
What are the two types of mGluR receptors that can affect synapses and lead to exaggerated functions when FMRP function is lost?
mGluR1 and mGluR5
What is mavoglurant and what is its role in synaptic function?
Mavoglurant is a selective mGluR5 antagonist that can affect NMDA receptors in learning and memory, leading to strengthening of synapses
What is LTP (long-term potentiation) and how is it achieved?
LTP is a persistent increase in synaptic strength produced by a burst of activity in the presynaptic neuron, often induced by tetanic stimulus
What is the role of NMDA receptors in the mechanisms of LTP?
NMDA receptors play a crucial role in the conversion of silent synapses to functional synapses and are required for the induction of LTP
What is LTD (long-term depression) and how does it differ from LTP?
LTD causes the withdrawal of AMPA receptors from the membrane, reducing sensitivity, while LTP enhances sensitivity by increasing the rate of receptor insertion and enhancing sensitivity to glutamate
What does glutamate LTD cause in terms of AMPA receptors?
It causes the withdrawal of AMPA receptors from the membrane and reduces sensitivity.
Where was the first discovery of LTD?
The first discovery of LTD was in the hippocampus, but it occurs in many different areas.
What is required for LTD in the Hippocampal CA1 region?
LTD in the Hippocampal CA1 region is postsynaptic and requires activation of NMDA receptors.
What are the two phases of LTD?
The two phases of LTD are ELTP (early LTP) and LLTP (late LTP).
What is the role of NMDA receptors in the induction phase of LTD?
NMDA receptors play an important role only in the induction phase of LTD.
What occurs in the expression phase of LTD?
In the expression phase of LTD, there is a resulting increase in synaptic strength measured by the influx of Ca2 activating protein kinases like CaMKII.
What happens in the brain slice during the study of LTD?
LTD is studied in brain slices where pyramidal neurons receive excitatory glutamatergic inputs from nerve terminals on dendritic spines.
How is induction phase of LTD characterized?
The induction phase of LTD occurs during and immediately after stimulation, involving NMDA receptors and Ca2 influx activating protein kinases.
What causes the rapid expansion of dendritic spines and insertion of more AMPA receptors in the spine membrane during LTD?
CaMKII remains activated even after Ca2 returns to baseline, causing rapid expansion of dendritic spines and insertion of more AMPA receptors in the spine membrane.
What is the role of BDNF in LTD?
Tetanic stimulus provokes the release of BDNF, which participates in ELTP (early LTP) during LTD.
What activates protein kinases, including CaMKII, to increase synaptic strength?
Influx of Ca2
What remains activated even after Ca2 levels return to baseline, causing rapid expansion of dendritic spines and insertion of more AMPA receptors?
CaMKII
What is released in response to a tetanic stimulus and participates in ELTP (early long-term potentiation)?
BDNF
What is the process of continuously moving neurotransmitter receptors into and out of the cell membrane?
Receptor trafficking
How is receptor insertion, specifically AMPA receptors, typically achieved in synaptic plasticity?
Exocytosis
What can last for days or months when produced in an animal and involves high levels of glutamate which can be toxic to nerve cells?
Long-term potentiation (LTP)
What hypothesis states that excessive exposure to glutamate can lead to damage or death of nerve cells, particularly at postsynaptic sites?
Excitotoxicity hypothesis
What type of cell death is triggered by strong activation of NMDA receptors and involves the bursting of the cell?
Necrosis by lysis
What type of cell death leads to disruption of the cell nucleus, DNA breakup, and eventual cell death without bursting?
Apoptosis
What is the term for the process where cells are cleared away by phagocytosis after cell death?
Apoptotic cell clearance
What is excitotoxicity triggered by in neuronal cell death?
Strong activation of NMDA receptors
Can cell death occur without NMDA receptor involvement?
Yes
How does necrosis by lysis occur in cell death?
After high concentrations of glutamate
What causes cell death by bursting of the cell?
Delayed excitotoxic reaction dependent on NMDA receptor activation
What is programmed cell death known as?
Apoptosis
What leads to disruption of the cell nucleus, DNA breakup, and cell death in apoptosis?
Apoptosis
How are cells cleared away in apoptosis?
By phagocytosis
What is another term for programmed necrosis?
Necroptosis
What type of receptors mediate excitotoxicity in the adult brain?
Extrasynaptic NMDA receptors
What is monosodium glutamate (MSG)?
Sodium salt of glutamate
Why does MSG not raise brain glutamate levels?
Because it doesn't penetrate the blood-brain barrier (BBB)
What is excitotoxic cell death mediated by in clinical medicine?
Consumption of domoic acid
What inhibitory amino acid transmitters are majorly involved in neuronal signaling?
GABA and glycine
What specific neurons manufacture GABA as a neurotransmitter?
GABAergic neurons
What enzyme synthesizes GABA from glutamate?
Glutamic acid decarboxylase (GAD)
What happens if there is a reduction in the synthesis of GABA?
It leads to convulsions
How is GABA removed from the extracellular space after synaptic release?
By GAT1, GAT2, and GAT3
What transporter is responsible for taking up glutamate into synaptic vesicles?
Vesicular GABA transporter (VGAT or VIAAT)
What else does the vesicular inhibitory amino acid transporter (VGAT or VIAAT) take up besides glutamate?
Glycine
What is expressed by GAT1 and GAT2?
GABA
What are the major inhibitory amino acid transmitters in the nervous system?
GABA and glycine
Which neurotransmitter serves as a neurotransmitter and is manufactured only by GABAergic neurons?
GABA
How is GABA synthesized from glutamate?
Glutamate is converted to GABA by the enzyme GAD (glutamic acid decarboxylase)
What substances block the synthesis of GABA?
Allylglycine, thiosemicarbazide, and 3-mercaptopropionic acid
What is the function of GABA in regulating excitability?
GABA regulates excitability by reducing synaptic transmission
What happens if there is a reduction in the synthesis of GABA?
It can lead to convulsions or seizures
What are the types of GABA transporters responsible for removing GABA from the extracellular space?
GAT1, GAT2, and GAT3
Where is GAT3 primarily found in the brain?
GAT3 is found only in astrocytes
What is the cellular mechanism for metabolizing and recycling GABA?
GABA breakdown occurs through the enzyme GABA aminotransferase (GABAT)
What byproduct is produced during the breakdown of GABA by GABAT?
1 molecule of glutamate is produced for every molecule of GABA being broken down
What is the irreversible inhibitor of GABAT?
Vigabatrin
How does vigabatrin affect GABA metabolism when administered?
It prevents GABA metabolism, leading to a buildup of GABA levels in the brain, used as an anticonvulsant
What enzyme converts glutamate produced by GABAT in astrocytes to glutamine?
Astrocytic glutamine synthetase
What is the final product of the breakdown of GABA by GABAT?
Succinate
What neurotransmitter is coreleased with other neurotransmitters in the brain?
GABA
What is the final product of synthesizing GABA in GABAergic neurons?
Succinate
How many glutamate molecules are produced as a byproduct for every molecule of GABA being broken down?
1
Where is glutamate produced by GABAT in astrocytes converted to glutamine?
Astrocytic glutamine synthetase
Where is glutamine transported back to, to be converted back to glutamate in neurons?
Neuron
What is the irreversible inhibitor of GABAT that prevents GABA metabolism?
Vigabatrin
What happens when Vigabatrin is administered in terms of GABA levels in the brain?
Buildup of GABA levels in the brain
What is Vigabatrin commonly used for in medicine?
Anticonvulsants
Besides GABA, what other neurotransmitters is GABA coreleased with?
Many others
Is GABA synthesized and coreleased by many neurons?
Yes
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Where does glycine function occur in the brainstem and spinal cord?
Brainstem and spinal cord
What neurotransmitters may inhibitory neurons in the brainstem and spinal cord release?
GABA, glycine, or a combination of both
Where is GABA found in the cortex, hippocampus, and substantia nigra?
Cortex, hippocampus, substantia nigra
What is the function of GABAergic cells in the hippocampus and cortex?
Interneurons
What type of cells use GABA as a transmitter in the cerebellar cortex?
Purkinje cells
What are the effects of spinocerebellar ataxias caused by degeneration and death of purkinje cells in the cerebellar cortex?
Ataxia, impaired balance, poor motor coordination
What do GABAa receptors target in the brain?
Ionotropic receptors
What do ion channels in GABAa receptors permit to move across the cell membrane?
Cl ions
What is the result of Cl ions moving from outside to inside the cell membrane in a GABAa receptor?
Inhibition of the postsynaptic cell, hyperpolarization, prevention of firing an action potential
How many subunits make up a GABAa receptor?
5 subunits: 2 alpha, 2 beta, and a gamma
What type of inhibition do extrasynaptic GABA receptors contribute to in the brain?
Tonic cellular inhibition
What is the significance of extrasynaptic GABA receptors in behavioral effects?
Contribute to sedating, sleep-promoting, and other behavioral effects of many non-Benzodiazepine positive allosteric modulators
Which subunits are affected by the administration of BDZ agonists on GABAa receptors?
Alpha 1,2,3,5 or alpha6, and two beta gamma 2 or delta subunits
What are the effects of high levels of muscimol, a GABAa receptor agonist?
Hyperthermia, pupil dilation, elevated mood, difficulties in concentration, anorexia, ataxia, catalepsy, and hallucinations
What drug competitively blocks the binding of GABA to GABAa receptors?
Bicuculline
What are the effects of pentylenetetrazol and picrotoxin on GABAa receptors?
Negatively modulate the receptor function by acting on a distinct site from the GABA binding site
What is the effect of convulsant drugs on GABAa receptor function?
Inhibit the function of the receptor by acting on sites distinct from the GABA binding site
What are some of the behavioral effects of non-BDZ positive allosteric modulators targeting alpha4, alpha5, alpha6, beta, gamma, and delta subunits?
Sedating, sleep-promoting, and other behavioral effects
Which substances have stimulatory and hallucinogenic qualities at high levels and can cause hyperthermia, pupil dilation, mood elevation, anorexia, ataxia, catalepsy, and hallucinations similar to LSD?
Muscimol
What effect does the competitive agonist bicuculline have on GABA receptors?
Blocks binding of GABA to GABAa receptor
How do convulsant drugs such as pentylenetetrazol and picrotoxin affect GABAa receptor function?
Inhibit GABAa receptor function by acting on a negative modulatory site
Which subunits of the GABAa receptor are sensitive to BDZs and require the presence of a gamma subunit and alpha a1, a2, a3, or a5 along with any beta subunit?
Not all GABAa receptors are sensitive to BDZs; they require the presence of a gamma subunit and alpha a1, a2, a3, or a5 along with any beta subunit
Which subunits of the GABAa receptor are responsible for sedating effects attributed to BDZs?
Alpha 1 subunits
Which subunits of the GABAa receptor are responsible for anxiolytic effects attributed to BDZs?
Alpha 2 and alpha 3 subunits
Which subunit of the GABAa receptor is most important for muscle relaxation?
Alpha 2 subunit
What is the role of barbiturates in potentiating GABA-mediated inhibition?
Enhancing GABA-mediated inhibition by potentiating GABAa receptor activity
How do neuroactive steroids (neurosteroids) interact with the GABAa receptor?
They interact with sites on the receptor distinct from the GABA binding sites
What are the subunits required in combination with the gamma subunit to form a functional GABAa receptor?
Alpha a1a2a3 or a5 along with any beta subunit
Which alpha subunit is responsible for sedating effects in GABAa receptors?
Alpha 1
Which alpha subunits are attributed to anxiolytic effects in GABAa receptors?
Alpha 2 and alpha 3
Which alpha subunit is most important for muscle relaxation in GABAa receptors?
Alpha 2
How do barbiturates potentiate GABA mediated inhibition in GABAa receptors?
By potentiating GABA mediated inhibition
What effects do ethanol have on GABAa receptor activity?
Enhance GABAa receptor activity
What is the role of neuroactive steroids (neurosteroids) in GABAa receptors?
They are steroid hormones synthesized in the brain that act locally on GABAa receptors
What happens at high levels of barbiturates, anesthetics, and neurosteroids with respect to GABAa receptors?
They can open the receptor channel without the presence of GABA
What do inverse agonists do in terms of GABAa receptors?
Negatively modulate the receptor and have opposite effects of benzodiazepines (BDZs)
What are endozepines and how do they modulate GABAa receptors?
Endogenous benzodiazepines that allosterically modulate GABAa receptors by acting at the same site as benzodiazepines
Describe the characteristics and function of GABAb receptors.
Metabotropic receptors that require 2 subunits, inhibit neuronal firing postsynaptically through K channel stimulation, and reduce neurotransmitter release presynaptically by inhibiting Ca2 channel opening
What is the role of agonists baclofen and saclofen in relation to GABAb receptors?
Agonist baclofen is used for muscle relaxing, while saclofen is a competitive agonist of GABAb receptors
How do anesthetics interact with GABAa receptors and what effects do they induce?
Anesthetics strongly enhance GABAa receptor activity, induce unconsciousness, block sensory awareness, and lack of pain sensitivity
What role does the extrasynaptic hippocampal alpha 5 receptor play in GABAa receptors?
It plays a role in amnesia
Terminals release neurotransmitters by:
Inhibiting Ca2+ channel opening
Both baclofen and saclofen are agonists for which receptor?
GABAb receptor
What do anesthetics and neurosteroids interact with to induce unconsciousness and block sensory awareness?
GABAa receptor
What is the role of extrasynaptic hippocampal alpha 5 receptor?
Plays a role in amnesia
What is the potential therapeutic value of negative allosteric modulators targeting alpha 5 containing GABAA receptors?
Cognitive enhancement
What are neurosteroids primarily known for?
Acting on signaling molecules in the nervous system
What are endogenous molecules that target allosteric binding sites on GABAa receptor?
Neurosteroids
Which neurosteroids are positive allosteric modulators of GABAa receptors?
ALLO, THDOC, and AS
What effects do negative modulators such as DHEAS and PS have on NMDA receptors?
Anxiogenic and proconvulsant effects
What is the significance of catamenial epilepsy in relation to seizures?
Seizures occurring during the menstrual cycle
What are the two types of catamenial epilepsy based on timing?
Type 1: periovulatory - time of ovulation; Type 2: perimenstrual - time of menstruation
What is Brexanolone?
A synthetic form of ALLO used for treating postpartum depression
What is the primary effect of GABAa receptors on epilepsy?
Recurrent convulsive and nonconvulsive seizures
What is hippocampal sclerosis characterized by?
Cell loss in the hippocampus
What is status epilepticus?
Episodes of repeated seizures where the patient can't recover from them
How do BDZs help in epilepsy treatment?
They help in managing seizures
What is catamenial epilepsy?
Seizures that occur during the menstrual cycle, with Type 1 occurring around the time of ovulation and Type 2 around the time of menstruation
What is brexanolone?
A synthetic form of ALLO used for treating postpartum depression
What is hippocampal sclerosis?
Cell loss in the hippocampus, often associated with epilepsy
What is status epilepticus?
Episodes of repeated seizures where the patient cannot recover from them
How do benzodiazepines (BDZs) help in epilepsy?
They enhance tonic inhibition by interacting with BDZ-insensitive extrasynaptic delta subunit on GABAA receptors
What is the role of excitotoxicity in epilepsy?
Excitotoxicity, mediated by NMDA receptors, contributes to neuronal damage in epilepsy
What is the relationship between anxiogenic and proconvulsant effects in epilepsy?
Anxiogenic and proconvulsant effects can exacerbate epilepsy and cognitive function
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