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Chapter 2 - Stem Cells in Nervous System Development and Regenerative Medicine
Study
1
Question
What are embryonic stem cells destined to become in the nervous system?
Answer
Neurons (nerve cells) and glial cells (supporting cells)
2
Question
What is the capacity of unspecialized stem cells to become any tissue or organ cell type, including blood cells, muscles, or neurons?
Answer
Pluripotent
3
Question
What can help control the differentiation of cell types in culture dishes?
Answer
Inserting genes or changing chemicals
4
Question
What are the potential benefits of using stem cells in drug development and understanding organism development?
Answer
Improving knowledge of organism development, understanding genes and molecular controls of differentiation, and efficient drug development
5
Question
In cell therapy, what type of stem cells are used to screen drugs to avoid toxic effects on cell types and organs?
Answer
Cell lines
6
Question
What could lost oligodendroglial cells in a rat model of human demyelinating disease be directed to form?
Answer
Specific classes of CNS neurons, extend axons, form synapses with target muscle, and replicate in the spinal cord
7
Question
Efforts have been made to replace inactive pancreatic beta cells in people with type 1 diabetes to restore what?
Answer
Normal levels of insulin
8
Question
What diseases have trials been conducted with adult stem cells for cell therapy?
Answer
Parkinson's disease, amyotrophic lateral sclerosis (ALS), macular degeneration, and severe burns
9
Question
Where are neural stem cells found in the brain?
Answer
Subventricular zone, lateral ventricle, and hippocampal dentate gyrus
10
Question
What is neurogenesis?
Answer
The birth of new nerve cells throughout the lifespan
11
Question
What can neural stem cells differentiate into?
Answer
Oligodendroglia and astrocytes
12
Question
What are induced pluripotent stem cells (iPS cells) created by?
Answer
Genetically reprogramming mature cells to develop characteristics of embryonic stem cells
13
Question
What is one application of induced pluripotent stem cells in drug development and testing?
Answer
Studied in patients undergoing heart surgery, injected in blood or in the injured heart to help heart function
14
Question
What is a challenge of using adult stem cells for therapy compared to embryonic stem cells?
Answer
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
15
Question
How does aging affect the amount and quality of stem cells in the body?
Answer
Older cells have decreased numbers, damaged DNA, and a shorter lifespan, making them less likely to be immune rejected
16
Question
What is required for genetic reprogramming to convert mature cells into induced pluripotent stem cells?
Answer
Viral vectors to deliver genetic material into the cells
17
Question
What structures support neurogenesis, the birth of new nerve cells throughout life span?
Answer
Lateral ventricle and hippocampal dentate gyrus
18
Question
What can neurogenesis differentiate into?
Answer
Oligodendroglia and astrocytes
19
Question
Why are nerve cells found in the hippocampus important?
Answer
Due to the mechanism of action of antidepressants
20
Question
What are induced pluripotent stem cells (IPS cells)?
Answer
Cells created by genetically reprogramming mature cells to develop characteristics of embryonic stem cells
21
Question
Where are IPS cells used in drug development and testing?
Answer
Some studies performed in patients undergoing heart surgery, inject in blood or in the injured heart to help heart function
22
Question
Why is it important to match cell donors when using IPS cells?
Answer
To prevent rejection by the immune system
23
Question
What is required for genetic reprogramming of adult cells?
Answer
Viral vectors to get genetic material into adult cells
24
Question
What can retrovirus vectors used for genetic reprogramming potentially produce?
Answer
Cancer
25
Question
What evidence shows reduced proliferation of brain stem cells in schizophrenia, depression, and bipolar disorder?
Answer
There is evidence showing reduced proliferation of brain stem cells in these conditions
26
Question
What do glial cells provide for neurons?
Answer
Metabolic support, protection, and insulation
27
Question
What are the principal functions of neurons?
Answer
To transmit information through electrical signaling over long distances
28
Question
What is the role of sensory neurons?
Answer
They are sensitive to environmental stimuli, convert physical stimuli and internal environment into electrical signals, and transmit information to circuits
29
Question
What are interneurons?
Answer
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
30
Question
What is the role of motor neurons?
Answer
To direct biobehavioral responses appropriate for the situation
chapter 7.pdf Flashcards
Study
1
Question
What is the key neurotransmitter in the peripheral nervous system (PNS)?
Answer
Acetylcholine (ACh)
2
Question
How is acetylcholine (ACh) synthesized in the body?
Answer
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.
3
Question
Where does choline, a precursor for acetylcholine, come from?
Answer
Choline comes from fat in the diet and is also produced in the liver.
4
Question
What controls the rate of acetylcholine (ACh) synthesis in neurons?
Answer
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.
5
Question
What is the role of the vesicular ACh transporter (VAChT) in neurons?
Answer
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.
6
Question
What are the effects of overactivity of acetylcholine (ACh) in the body?
Answer
Muscle pain in the abdomen and chest, tremors, nausea, vomiting, salivation, and copious sweating can occur due to overactivity of ACh.
7
Question
How does botulism affect neurotransmission?
Answer
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.
8
Question
What is the role of acetylcholinesterase (AChE) in the body?
Answer
AChE breaks down neurotransmitter into choline and acetic acid. There are 3 forms of AChE: soluble G4, membrane-bound G4, and A12.
9
Question
What is the function of the VAChT vesicular ACh transporter?
Answer
Transport ACh in the vesicle membrane
10
Question
What is vesamicol and how does it affect ACh levels?
Answer
Vesamicol blocks the VAChT transporter, increasing the level of ACh in the cytoplasm but decreasing vesicular ACh
11
Question
What are the symptoms of overactivity of ACh at synapses in the PNS, as seen in Latrodectus mactans envenomation?
Answer
Muscle pain in the abs, chest tremors, nausea, vomiting, salivation, and copious sweating
12
Question
How does botulism affect ACh release and what symptoms does it cause?
Answer
Botulism inhibits ACh release, leading to muscular paralysis. Symptoms include muscle weakness and possible paralysis
13
Question
What is acetylcholinesterase (AChE) and what is its function?
Answer
AChE breaks down neurotransmitters into choline and acetic acid. It prevents muscle receptors from becoming desensitized to the neurotransmitter
14
Question
What are the three forms of AChE and where are they found?
Answer
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
15
Question
How do drugs that block AChE affect neurotransmission?
Answer
Drugs that block AChE prevent the inactivation of ACh, leading to increased postsynaptic effects of the transmitter
16
Question
What are some examples of drugs used for dementia that are AChE inhibitors?
Answer
Donepezil, Rivastigmine, and Galantamine are synthetic compounds that enter the brain and inhibit AChE activity
17
Question
What is the function of the AChE inhibitor pyridostigmine and physostigmine?
Answer
They are used to reverse AChE inhibitors, binding temporarily to the enzyme protein to inhibit its action
18
Question
How do organophosphorus compounds like sarin and soman affect AChE activity?
Answer
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
19
Question
What is the mechanism of drugs used for dementia like Donepezil, Rivastigmine, and Galantamine?
Answer
They block AChE to prevent the inactivation of ACh and increase the postsynaptic effects of the transmitter.
20
Question
What is the role of AChE inhibitors like pyridostigmine and Physostigmine?
Answer
They reversibly inhibit AChE activity by binding temporarily to the enzyme protein, inhibiting its action until the drug dissociates and ACh breakdown is restored.
21
Question
What is the mechanism of action of organophosphorus compounds like Sarin and Soman?
Answer
They irreversibly inhibit AChE activity, leading to rapid accumulation of ACh and overstimulation of cholinergic synapses throughout the CNS and PNS.
22
Question
What are the symptoms of organophosphate poisoning due to AChE inhibition?
Answer
Profuse sweating, salivation, vomiting, loss of bladder control, loss of bowel control, convulsions, and ultimately death through asphyxiation due to muscle paralysis.
23
Question
What is the role of the basal forebrain cholinergic system?
Answer
It is the origin of dense cholinergic innervation of the cerebral cortex and is involved in regulating cognitive functions.
24
Question
What is the function of anticholinergic drugs like Norflex, Cogentin, Artane, Kemadrin, and Biperiden?
Answer
They are used for Parkinson's disease to counteract excessive acetylcholine activity and restore balance to the cholinergic system.
25
Question
Which neurotransmitter is affected by AChE inhibitors and anticholinergic agents?
Answer
Acetylcholine (ACh).
26
Question
What autoimmune disorder is associated with muscle weakness and affects the neuromuscular junction?
Answer
Myasthenia gravis.
27
Question
What is the role of ChAT and AChE in myasthenic syndromes?
Answer
Mutations in the genes encoding ChAT or AChE can lead to myasthenic syndromes, affecting the release, breakdown, and activation of acetylcholine.
28
Question
Where are the preganglionic neurons of the sympathetic and parasympathetic branches located?
Answer
They are located within the CNS and send axons to autonomic ganglia.
29
Question
What results from mutations in the genes that encode either ChAT or AChE?
Answer
Myasthenic syndromes
30
Question
Where are the preganglionic neurons located for both the sympathetic and parasympathetic branches of the autonomic nervous system?
Answer
Within the CNS, sending axons to autonomic ganglia
chapters 4 & 8.pdf Flashcards
Study
1
Question
What are behavioral measures important for in behavioral pharmacology?
Answer
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.
2
Question
What are the advantages of animal studies in pharmacology?
Answer
Rigorous control, ability to administer drugs, similarity in brains and behavior to humans, and living conditions.
3
Question
What is correlational studies in behavioral pharmacology?
Answer
The connection between two events that appear related but cannot be assumed to be cause and effect.
4
Question
What is predictive validity in animal studies?
Answer
Measures how closely results from animal tests predict clinically useful effects in humans.
5
Question
What is construct validity in animal studies?
Answer
The extent to which animal measurement tools measure human characteristics of interest.
6
Question
What is a vehicle solution in pharmacology?
Answer
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.
7
Question
What is a positive control in pharmacology?
Answer
An experimental control procedure where a well-characterized active treatment is compared to an experimental treatment.
8
Question
What is predictive validity in animal testing?
Answer
Predictive validity measures how closely results from animal tests predict clinically useful effects in humans.
9
Question
What is construct validity in animal testing?
Answer
Construct validity is the extent to which animal measurement tools measure human characteristics of interest.
10
Question
What is a negative control in animal testing?
Answer
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.
11
Question
What is a positive control in animal testing?
Answer
A positive control is an experimental control procedure where a well-characterized active treatment is compared to an experimental treatment.
12
Question
What are the characteristics of an ideal animal behavioral test?
Answer
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.
13
Question
What is the open field test in animal behavior testing?
Answer
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.
14
Question
What is operant conditioning in animal behavior testing?
Answer
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.
15
Question
What is an operant chamber in animal behavior testing?
Answer
An operant chamber is a controlled environment where animals are subjected to a schedule of reinforcement in operant conditioning experiments.
16
Question
What measures motor activity and is used to identify drugs that produce sleep, sedation, or motor impairment?
Answer
Open field test
17
Question
What behavior is indicative of anxiety-like behavior in animals during the open field test?
Answer
Low activity and high fecal counts
18
Question
What method is used to evaluate behaviors related to learning and memory by controlling consequences?
Answer
Operant conditioning
19
Question
What is a fixed ratio reinforcement schedule in operant conditioning?
Answer
Reinforcement delivered after a fixed number of responses
20
Question
What does changing the number of times needed to press in a fixed ratio reinforcement schedule indicate?
Answer
How hard the subject is willing to work for reinforcement
21
Question
What is an interval reinforcement schedule in operant conditioning?
Answer
Availability of reinforcement after a certain amount of time has elapsed
22
Question
What is measured in the tail flick test to assess analgesia in animals?
Answer
The latency between the onset of the stimulus and the animal removing its tail
23
Question
What is the hot plate test used for in drug evaluation?
Answer
Assessing analgesia based on the latency between an increase
24
Question
What is the tail flick test used for?
Answer
Measuring analgesia by correlating the latency between onset of stimulus and animal removal of the tail with pain intensity
25
Question
What is the hot plate test used for?
Answer
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
26
Question
What is operant analgesia testing?
Answer
Subject learns to turn off foot shock by pressing a lever; used to evaluate effectiveness of analgesic drugs by raising the electric shock threshold
27
Question
What is aversive threshold in operant analgesia testing?
Answer
The lowest shock intensity at which the animal first presses the lever; used for mild analgesics like aspirin
28
Question
What is the purpose of tests of learning and memory in experimental research?
Answer
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
29
Question
What is the T-maze or multiple T-maze used for in research?
Answer
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
30
Question
What is the aversive threshold used for?
Answer
Mild analgesics like aspirin
chapters 4 & 8.pdf Flashcards
Study
1
Question
What is the Sucrose preference test used to measure?
Answer
Anhedonia
2
Question
What do animals show a strong preference for in the Sucrose preference test?
Answer
Sweetened solution
3
Question
What is an accurate indicator of abuse potential in humans according to chronic antidepressant treatment?
Answer
Self-administration method
4
Question
What do animals readily self-administer to indicate abuse potential in humans?
Answer
Morphine, cocaine, and amphetamine
5
Question
What is the most valid model of drug seeking in humans according to chronic antidepressant treatment?
Answer
Breakpoint
6
Question
What does the Breakpoint measure in drug seeking behavior?
Answer
The effort required exceeds the reinforcing value
7
Question
What brain circuits are needed for reinforcement of behavior according to chronic antidepressant treatment?
Answer
Electrical self-stimulation
8
Question
What do animals work to stimulate in brain circuits needed for reinforcement of behavior?
Answer
Clusters of neurons
9
Question
What do morphine and heroin increase in response to low levels of electrical stimulation according to chronic antidepressant treatment?
Answer
Brain reinforcement mechanism
10
Question
What is conditioned place preference based on?
Answer
Classically conditioned association between drug effect and environment
11
Question
In conditioned place preference, where does the animal spend more time if the drug is rewarding?
Answer
In the compartment associated with the rewarding drug
12
Question
What are drugs as discriminative stimuli used for in operant tasks?
Answer
To signal reinforcement for a subject
13
Question
What do automated quantification of behavior tools provide in psychopharmacological research?
Answer
Computer version evolving technology used to discern a wide array of behaviors
14
Question
What is the goal of translational research in psychopharmacology?
Answer
To transform discoveries from basic neuroscience research into clinical applications for treating mental and neurological disorders
15
Question
What does a Stop signal task measure in behavioral research?
Answer
Impulsivity
16
Question
What is the process by which a drug is rewarding if the animal spends more time in that compartment compared to the aversive drug?
Answer
Conditioned place preference
17
Question
What is the term for a stimulus that signals reinforcement for a subject in an operant task?
Answer
Discriminative stimulus
18
Question
What type of research involves transforming discoveries from basic neuroscience research into clinical applications for treating mental and neurological disorders?
Answer
Translational research
19
Question
What is the procedure used to measure impulsivity that involves the failure of cortical control mechanisms to suppress inappropriate responses?
Answer
Stop signal task
20
Question
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?
Answer
Stereotaxic surgery
21
Question
What type of lesions are created by applying heat to the cells near the tip of an insulated electrode?
Answer
Electrolytic lesions
22
Question
How are specific neurotoxins injected to identify the brain area responsible for drug-induced changes in behavior?
Answer
Directly into the brain
23
Question
What device is used to identify lesions in the brain through MRI or CT scans?
Answer
Lesioning and microinjection Stereotaxic device
24
Question
What is used to insulate the electrode and provide stops at the tip?
Answer
Insulated electrode
25
Question
How do electrolytic lesions destroy tissue in the brain?
Answer
By destroying cell bodies, dendrites, and axons near the tip of the electrode
26
Question
What is a neurotoxin and how is it used in neuroscience research?
Answer
A chemical that damages nerve cells, injected via cannula to destroy cells; used to identify brain areas responsible for drug-induced changes in behavior
27
Question
What method is used to measure neurotransmitter release in the brain during active behavior?
Answer
Microdialysis
28
Question
What is the purpose of artificial CSF being pumped through a microdialysis cannula during microdialysis?
Answer
To sample material in the extracellular space at precise sites
29
Question
What technique separates a sample into parts to determine the concentration of molecules of interest during microdialysis?
Answer
HPLC (High-Performance Liquid Chromatography)
30
Question
What does invivo voltammetry measure in freely moving animals?
Answer
Neurochemicals in the extracellular fluid
chapters 4 & 8.pdf Flashcards
Study
1
Question
What imaging technique increases resolution and provides a 3D image of the brain by placing the head in a cylindrical x-ray tube?
Answer
Computerized tomography (CT)
2
Question
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?
Answer
Magnetic resonance imaging (MRI)
3
Question
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?
Answer
Magnetic resonance spectroscopy (MRS)
4
Question
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?
Answer
Diffusion tensor imaging (DTI)
5
Question
What imaging technique localizes radioactively labeled materials injected into living humans, maps their distribution, and tracks gamma photons to locate their origin?
Answer
Positron emission tomography (PET)
6
Question
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?
Answer
Single photon emission computerized tomography (SPECT)
7
Question
What imaging technique detects increases in blood oxygenation caused by cell firing, providing anatomical and functional information?
Answer
Functional magnetic resonance imaging (fMRI)
8
Question
What is used to map the distribution of the brain but does not create images of the brain?
Answer
Isotopes that decay fast
9
Question
What can be administered to visualize brain activity and reflect glucose usage, oxygen usage, and blood flow?
Answer
Radioactively labeled drugs or ligands
10
Question
What technique allows for mapping brain areas with increased glucose and blood flow by tracking gamma photons?
Answer
Single Photon Emission Computerized Tomography (SPECT)
11
Question
What does fMRI detect increases in, caused by cell firing?
Answer
Blood oxygenation
12
Question
What does BOLD imaging provide in fMRI?
Answer
Anatomical and functional information along with a detailed image
13
Question
What does resting-state fMRI (rsfMRI) monitor in the brain when an individual is awake but not actively doing a task requiring attention?
Answer
Connectivity among brain regions
14
Question
What network includes the posterior cingulate cortex, medial PFC, ventral anterior cingulate cortex, and parts of the parietal cortex?
Answer
Default Mode Network
15
Question
What does pharmacological MRI (phMRI) analyze in drug development?
Answer
Change in brain function after drug administration and shows the location of drug action in the CNS
16
Question
What is EEG (Electroencephalography) used for in brain activity monitoring?
Answer
Detect electrical events in real time
17
Question
What is qEEG (Quantitative EEG) used for in brain analysis?
Answer
Computerized analysis to evaluate large complex data collected in an EEG
18
Question
What does ERP (Event-Related Potentials) visualize?
Answer
Processing of cognitive events
19
Question
What is phMRI and how is it related to fMRI?
Answer
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).
20
Question
What is qEEG and how is it used in personalized medicine?
Answer
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.
21
Question
What are ERPs in the context of EEG?
Answer
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.
22
Question
What is the CRISPR-Cas9 system used for in genetic engineering?
Answer
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.
23
Question
What is somatic genetic engineering?
Answer
Somatic genetic engineering affects the somatic cells of treated individuals, making targeted genetic modifications in non-reproductive cells.
24
Question
What is CRISPR?
Answer
Clustered Regularly Interspaced Short Palindromic Repeats, a technology used for genetic editing
25
Question
What is the role of guide RNA in CRISPR?
Answer
It identifies the genomic sequences to be modified by the Cas9 nuclease
26
Question
How does CRISPR work in gene editing?
Answer
Cas9 nuclease cuts out specified sections of DNA and new DNA is inserted, altering gene expression
27
Question
What is somatic genetic engineering?
Answer
It affects somatic cells of treated individuals, not passed on to offspring
28
Question
What is human germline engineering?
Answer
It edits and modifies the genome in gametes, affecting future generations
29
Question
What are Knockin mice?
Answer
Mice with an inserted gene that is slightly different from the wildtype, producing a modified protein
30
Question
What are Transgenic mice used for?
Answer
To study genetic disorders and ascertain the functional role of modified genes
chapters 4 & 8.pdf Flashcards
Study
1
Question
What are the two NTS required to stimulate the NMDA receptor and open the ion channel?
Answer
Glutamate and glycine
2
Question
Which receptor sticks out into the extracellular space?
Answer
NMDA receptor
3
Question
What binds to and activates the glycine binding site on the NMDA receptor?
Answer
D-serine
4
Question
What blocks the NMDA receptor channel when resting and opens when the membrane is depolarized?
Answer
Mg2
5
Question
What type of agonist is memantine in relation to the NMDA receptor?
Answer
Uncompetitive agonist
6
Question
Which antagonist can block both AMPA and kainate receptors?
Answer
NBQX
7
Question
What is the function of mGluR1 and mGluR5 in the mGluR group 1?
Answer
Mediate excitatory responses by activating phosphoinositide second messenger systems
8
Question
Where are mGluR2 and mGluR3 located in the mGluR group 2?
Answer
Presynaptic
9
Question
What is the function of Group 3 mGluR4, mGluR6, mGluR7, and mGluR8 in the metabotropic receptor system?
Answer
Signal by inhibiting cyclic adenosine monophosphate (cAMP) formation
10
Question
What is the mechanism of action of antagonist NBQX?
Answer
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.
11
Question
How are metabotropic receptors classified based on second messenger systems?
Answer
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.
12
Question
What is Fragile X syndrome (FXS) and its underlying cause?
Answer
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.
13
Question
What is the role of mGluR1 and mGluR5 in Fragile X syndrome?
Answer
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.
14
Question
What is the function of mavoglurant?
Answer
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).
15
Question
What are the two types of mGluR receptors that can affect synapses and lead to exaggerated functions when FMRP function is lost?
Answer
mGluR1 and mGluR5
16
Question
What is mavoglurant and what is its role in synaptic function?
Answer
Mavoglurant is a selective mGluR5 antagonist that can affect NMDA receptors in learning and memory, leading to strengthening of synapses
17
Question
What is LTP (long-term potentiation) and how is it achieved?
Answer
LTP is a persistent increase in synaptic strength produced by a burst of activity in the presynaptic neuron, often induced by tetanic stimulus
18
Question
What is the role of NMDA receptors in the mechanisms of LTP?
Answer
NMDA receptors play a crucial role in the conversion of silent synapses to functional synapses and are required for the induction of LTP
19
Question
What is LTD (long-term depression) and how does it differ from LTP?
Answer
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
20
Question
What does glutamate LTD cause in terms of AMPA receptors?
Answer
It causes the withdrawal of AMPA receptors from the membrane and reduces sensitivity.
21
Question
Where was the first discovery of LTD?
Answer
The first discovery of LTD was in the hippocampus, but it occurs in many different areas.
22
Question
What is required for LTD in the Hippocampal CA1 region?
Answer
LTD in the Hippocampal CA1 region is postsynaptic and requires activation of NMDA receptors.
23
Question
What are the two phases of LTD?
Answer
The two phases of LTD are ELTP (early LTP) and LLTP (late LTP).
24
Question
What is the role of NMDA receptors in the induction phase of LTD?
Answer
NMDA receptors play an important role only in the induction phase of LTD.
25
Question
What occurs in the expression phase of LTD?
Answer
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.
26
Question
What happens in the brain slice during the study of LTD?
Answer
LTD is studied in brain slices where pyramidal neurons receive excitatory glutamatergic inputs from nerve terminals on dendritic spines.
27
Question
How is induction phase of LTD characterized?
Answer
The induction phase of LTD occurs during and immediately after stimulation, involving NMDA receptors and Ca2 influx activating protein kinases.
28
Question
What causes the rapid expansion of dendritic spines and insertion of more AMPA receptors in the spine membrane during LTD?
Answer
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.
29
Question
What is the role of BDNF in LTD?
Answer
Tetanic stimulus provokes the release of BDNF, which participates in ELTP (early LTP) during LTD.
30
Question
What activates protein kinases, including CaMKII, to increase synaptic strength?
Answer
Influx of Ca2
chapters 4 & 8.pdf Flashcards
Study
1
Question
Where does glycine function occur in the brainstem and spinal cord?
Answer
Brainstem and spinal cord
2
Question
What neurotransmitters may inhibitory neurons in the brainstem and spinal cord release?
Answer
GABA, glycine, or a combination of both
3
Question
Where is GABA found in the cortex, hippocampus, and substantia nigra?
Answer
Cortex, hippocampus, substantia nigra
4
Question
What is the function of GABAergic cells in the hippocampus and cortex?
Answer
Interneurons
5
Question
What type of cells use GABA as a transmitter in the cerebellar cortex?
Answer
Purkinje cells
6
Question
What are the effects of spinocerebellar ataxias caused by degeneration and death of purkinje cells in the cerebellar cortex?
Answer
Ataxia, impaired balance, poor motor coordination
7
Question
What do GABAa receptors target in the brain?
Answer
Ionotropic receptors
8
Question
What do ion channels in GABAa receptors permit to move across the cell membrane?
Answer
Cl ions
9
Question
What is the result of Cl ions moving from outside to inside the cell membrane in a GABAa receptor?
Answer
Inhibition of the postsynaptic cell, hyperpolarization, prevention of firing an action potential
10
Question
How many subunits make up a GABAa receptor?
Answer
5 subunits: 2 alpha, 2 beta, and a gamma
11
Question
What type of inhibition do extrasynaptic GABA receptors contribute to in the brain?
Answer
Tonic cellular inhibition
12
Question
What is the significance of extrasynaptic GABA receptors in behavioral effects?
Answer
Contribute to sedating, sleep-promoting, and other behavioral effects of many non-Benzodiazepine positive allosteric modulators
13
Question
Which subunits are affected by the administration of BDZ agonists on GABAa receptors?
Answer
Alpha 1,2,3,5 or alpha6, and two beta gamma 2 or delta subunits
14
Question
What are the effects of high levels of muscimol, a GABAa receptor agonist?
Answer
Hyperthermia, pupil dilation, elevated mood, difficulties in concentration, anorexia, ataxia, catalepsy, and hallucinations
15
Question
What drug competitively blocks the binding of GABA to GABAa receptors?
Answer
Bicuculline
16
Question
What are the effects of pentylenetetrazol and picrotoxin on GABAa receptors?
Answer
Negatively modulate the receptor function by acting on a distinct site from the GABA binding site
17
Question
What is the effect of convulsant drugs on GABAa receptor function?
Answer
Inhibit the function of the receptor by acting on sites distinct from the GABA binding site
18
Question
What are some of the behavioral effects of non-BDZ positive allosteric modulators targeting alpha4, alpha5, alpha6, beta, gamma, and delta subunits?
Answer
Sedating, sleep-promoting, and other behavioral effects
19
Question
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?
Answer
Muscimol
20
Question
What effect does the competitive agonist bicuculline have on GABA receptors?
Answer
Blocks binding of GABA to GABAa receptor
21
Question
How do convulsant drugs such as pentylenetetrazol and picrotoxin affect GABAa receptor function?
Answer
Inhibit GABAa receptor function by acting on a negative modulatory site
22
Question
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?
Answer
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
23
Question
Which subunits of the GABAa receptor are responsible for sedating effects attributed to BDZs?
Answer
Alpha 1 subunits
24
Question
Which subunits of the GABAa receptor are responsible for anxiolytic effects attributed to BDZs?
Answer
Alpha 2 and alpha 3 subunits
25
Question
Which subunit of the GABAa receptor is most important for muscle relaxation?
Answer
Alpha 2 subunit
26
Question
What is the role of barbiturates in potentiating GABA-mediated inhibition?
Answer
Enhancing GABA-mediated inhibition by potentiating GABAa receptor activity
27
Question
How do neuroactive steroids (neurosteroids) interact with the GABAa receptor?
Answer
They interact with sites on the receptor distinct from the GABA binding sites
28
Question
What are the subunits required in combination with the gamma subunit to form a functional GABAa receptor?
Answer
Alpha a1a2a3 or a5 along with any beta subunit
29
Question
Which alpha subunit is responsible for sedating effects in GABAa receptors?
Answer
Alpha 1
30
Question
Which alpha subunits are attributed to anxiolytic effects in GABAa receptors?
Answer
Alpha 2 and alpha 3