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Chapter 2 - Stem Cells in Nervous System Development and Regenerative Medicine
Study
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
chapter 7.pdf Flashcards
Study
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
chapters 4 & 8.pdf Flashcards
Study
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
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
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
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
chapters 4 & 8.pdf Flashcards
Study
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
