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Questions and Answers
What intrinsic property influences the release probability of catecholamines?
What intrinsic property influences the release probability of catecholamines?
What process primarily terminates the action of catecholamines in the bloodstream?
What process primarily terminates the action of catecholamines in the bloodstream?
Which type of receptor change can affect the sensitivity of postsynaptic sites to catecholamines?
Which type of receptor change can affect the sensitivity of postsynaptic sites to catecholamines?
Which medication is recognized as the most widely prescribed antidepressant?
Which medication is recognized as the most widely prescribed antidepressant?
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How do tricyclic antidepressants primarily function in the context of neurotransmitter reuptake?
How do tricyclic antidepressants primarily function in the context of neurotransmitter reuptake?
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What role does monoamine oxidase (MAO) play in neurotransmitter metabolism?
What role does monoamine oxidase (MAO) play in neurotransmitter metabolism?
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Which of the following actions does cocaine perform regarding neurotransmitters?
Which of the following actions does cocaine perform regarding neurotransmitters?
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What genetic polymorphism is related to the regulation of dopamine in the prefrontal cortex and associated with various psychiatric disorders?
What genetic polymorphism is related to the regulation of dopamine in the prefrontal cortex and associated with various psychiatric disorders?
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What is the role of autoreceptors in catecholaminergic synapses?
What is the role of autoreceptors in catecholaminergic synapses?
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How does the activation of D2 receptors affect neurotransmission?
How does the activation of D2 receptors affect neurotransmission?
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What effect does reserpine have on dopamine levels?
What effect does reserpine have on dopamine levels?
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Which neurotransmitter is primarily increased by amphetamines?
Which neurotransmitter is primarily increased by amphetamines?
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What is one mechanism by which amphetamines affect neurotransmitter transport?
What is one mechanism by which amphetamines affect neurotransmitter transport?
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What is the beneficial effect of D2 receptor blockade in the mesolimbic system?
What is the beneficial effect of D2 receptor blockade in the mesolimbic system?
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Which receptor type is involved in negative feedback regulation of norepinephrine release in the CNS?
Which receptor type is involved in negative feedback regulation of norepinephrine release in the CNS?
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How does TAAR1 modulation affect dopamine neuron firing?
How does TAAR1 modulation affect dopamine neuron firing?
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What determines the rate of DOPA synthesis in norepinephric neurons of the Locus coeruleus?
What determines the rate of DOPA synthesis in norepinephric neurons of the Locus coeruleus?
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What role does the vesicular monoamine transporter (VMAT2) play in catecholamine storage?
What role does the vesicular monoamine transporter (VMAT2) play in catecholamine storage?
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How does chronic use of certain stimulant drugs affect dopamine transport?
How does chronic use of certain stimulant drugs affect dopamine transport?
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Which of the following statements about tyrosine hydroxylase (TH) is true?
Which of the following statements about tyrosine hydroxylase (TH) is true?
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What effect do drugs like reserpine have on catecholamines?
What effect do drugs like reserpine have on catecholamines?
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Which factor triggers an increase in the expression of TH in norepinephric neurons?
Which factor triggers an increase in the expression of TH in norepinephric neurons?
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How does the phosphorylation of TH in dopaminergic neurons affect catecholamine synthesis?
How does the phosphorylation of TH in dopaminergic neurons affect catecholamine synthesis?
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Which of the following is a target of psychotropic drugs related to catecholamine storage?
Which of the following is a target of psychotropic drugs related to catecholamine storage?
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Study Notes
Neurochemical System
- Neurotransmitters are more diverse and their release is more complex than originally thought
- There are approximately 50 known neurotransmitters, potentially up to 100
- Neurotransmitters are often released from presynaptic sites, but can also be released from other sites
- Chemical signals are the primary mode of communication between neurons
- Neurotransmitter synthesis, release, and degradation are tightly controlled by various molecular mechanisms.
Criteria to define Neurotransmitters.
- Classical Neurotransmitters (NTs) are synthesized within the neuron from which they are released
- They are identifiable substances that can be characterized chemically or pharmacologically
- Exogenous application of the NT should elicit changes in the postsynaptic neuron(mimic the effects of stimulating the presynaptic neuron)
- NTs should act on specific receptors, whose action is blocked by antagonists or by genetic ablation
- There should be an active mechanism for terminating NT action
Major Classes of Neurotransmitters.
- Monoamines: Catecholamines, serotonin, melatonin
- Amino acids: Glutamate, GABA, glycine
- Peptide transmitters: Endorphins, somatostatin, oxytocin
- Acetylcholine: An organic compound released at the neuromuscular junction
- Gasotransmitters: Nitric oxide (NO), carbon monoxide (CO)
- Endocannabinoids: Lipid transmitters involved in retrograde neurotransmission
Regulation of the Monoamines (Catecholamines)
- Monoamine neurotransmitters contain an amino group connected to an aromatic ring via a two-carbon chain
- Monoaminergic systems are involved in regulating cognitive processes such as emotion, arousal, and memory
- Classical monoamines:
- Imidazoleamines
- Indolamines
- Histamine
- Serotonin (5-HT)
- Catecholamines:
- Dopamine (DA)
- Epinephrine (Epi = adrenaline)
- Norepinephrine (NE = noradrenaline)
Dopaminergic Projection System in the Brain.
- Major nuclei:
- Substantia nigra → striatum
- Ventral tegmental area → frontal and cingulate cortex, accumbens
- Arcuate nucleus → pituitary
Norepinephrine and Epinephrine Projection Systems.
- Norepinephrine cells are located in the medulla and pons
- Epinephrine cells are located in two nuclei in the medulla
Serotonin Projections in the Brain.
- Neuroanatomical projection tracts exist from caudal raphe nuclei, rostral raphe nuclei, and the median raphe nucleus to various brain regions
Catecholamines (Dopamine, Norepinephrine, Epinephrine)
- Catecholamines are organic compounds derived from tyrosine
- Expression of specific biosynthetic enzymes defines neuronal identity (i.e., neurons only express enzymes needed for the neurotransmitter they release)
In Situ Hybridization (ISH)
- ISH is used to detect and localize specific DNA or RNA fragments within chromosome preparations, fixed cells, or tissue sections
- The technique involves hybridizing probes to target RNA in a series.
- Probes attach to complementary sequences within the target DNA or mRNA.
Immunohistochemistry/Immunofluorescence/Immunostaining
- Techniques to examine tissues with antibodies
- Methods for visualizing proteins and other molecules in tissue samples
Immunohistochemistry Combined with Fluorescent Reporter
- Techniques used to visualize specific proteins and molecules in brain tissue
- Methods include using antibodies that stain for the proteins being investigated
Distribution of TH and GAD1 mRNA in the Mouse Brain
- In situ hybridization using probes for TH and GAD1 mRNA shows distinct distributions indicating different cell types in the brain
"Birth and Death" of Classical Neurotransmitters (NTs)
- NTs, from synthesis to degradation, have tightly regulated steps via molecular mechanisms and signaling pathways
Regulation of Catecholamines
- 1. Biosynthesis: The amount and activity of tyrosine hydroxylase (TH) determine the rate of dopamine synthesis; TH expression and activity increase in response to demand for catecholamines
- 2. Storage: Catecholamines are stored in vesicles; transported into vesicles by the vesicular monoamine transporter (VMAT2).
- 3. Release and activation of postsynaptic receptors: Action potentials trigger calcium influx, which triggers synaptic vesicle fusion and neurotransmitter release, activating postsynaptic receptors. Molecular changes in postsynaptic receptors affect their activation and response
- 4. Inactivation: Released NTs are rapidly removed through re-uptake by transporters/enzymes (e.g., monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT))
- 5. Autoreceptors and feedback loops: Autoreceptors on presynaptic neurons provide feedback mechanisms to regulate NT synthesis, release, and firing.
Regulation of Serotonin
- The synthesis and regulation of serotonin are similar to catecholamines
- Serotonin is stored in vesicles with VMAT2.
- Autoreceptors, including 5-HT1A and 5-HT1B, play critical roles in regulating serotonin synthesis and release and signal pathways are involved in the pathophysiology of depression
Serotonin and Antidepressant Drugs
- Reuptake of serotonin (5-HT) by serotonin transporter (SERT) is a major mechanism for terminating 5-HT action
- Selective serotonin reuptake inhibitors (SSRIs) are a common type of antidepressant that target SERT
- Similar to catecholamines, serotonin can be inactivated by MAO; therefore, MAO inhibitors may indirectly have effects on serotonin regulation
How Ecstasy (MDMA) Works
- Ecstasy disrupts the transport of serotonin into vesicles within presynaptic neurons
- Serotonin is released into the synapse and its reuptake is blocked, causing elevated levels of serotonin in the synaptic cleft.
Amino Acid Transporters: GABA and Glutamate
- GABA and glutamate are the most prevalent amino acid neurotransmitters in the brain
- Their biosynthetic pathways are interlinked
- These amino acids are inactivated by reuptake
GABA and Glutamate Reuptake
- GABA is inactivated by reuptake via GABA transporters (GAT1, GAT3) and the vesicular GABA transporter (VGAT).
- Glutamate is inactivated by glutamate transporters (EAAT1–EAAT5)
Glutamate Transporters
- EAATs/VGLUTs are critical for glutamate regulation
Excitatory-Inhibitory Balance
- The balance of excitatory (glutamate) and inhibitory (GABA) neurotransmission is vital for normal brain function
Antibody labeling for Inhibitory Synapses
- VGAT is the appropriate antibody to label inhibitory synapses
Fusion Proteins for Synapse Quantification
- Fusion proteins (e.g., GFP-tagged proteins) are useful tools for precise quantification of synapses in animal models, but not in humans
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Description
Explore the intricate world of neurotransmitters with this quiz on their diversity, synthesis, and communication methods between neurons. Understand the criteria that define classical neurotransmitters and their functional roles in the nervous system. Test your knowledge on the mechanisms that regulate these chemical signals.
