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Neuropsych > 3 - Neurotransmitters > Flashcards

3 - Neurotransmitters Flashcards

1
Q

Classification of Neurotransmitters

A
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2
Q

Selected Neuropeptide Transmitters

A
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3
Q

List the neurotransmitters in the classifical classification

A

Acetylcholine

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4
Q

List the neurotransmitters that are monoamines

A

Epinephrine
Norepinephrine
Dopamine
Serotonin
Histamine

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5
Q

list the neurotransmitters that are amino acids

A

GABA (𝛾-aminobutyric acid)
Glycine
Glutamate and Aspartate

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6
Q

List the neurotransmitters that are soluble gases

A

nitric oxide (NO)
carbon monoxide (CO)

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7
Q

list neurotransmitters that are lipids (endocannabinoids)

A

Anandamide

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8
Q

List the large molecule neuropeptide families

A

hypothalamic peptides
pituitary peptide hormones
brain-gut peptides
brain-endocrine peptides
brain-skin peptides
Trophic factors

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9
Q

Neuropeptide Transmitters - list the hypothalamic releasing hormones

A

thyrotropin releasing hormone
luteinizing hormone releasing
somatostatin

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10
Q

Neuropeptide Transmitters - list the pituitary peptides

A

adrenocorticotropic hormone
Ξ²-endorphin
⍺-melanocyte stimulating hormone
prolactin
luteinizing hormone
growth hormone
oxytocin
vasopressin
thyrotropin

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11
Q

Neuropeptide Transmitters - List the Gut-Brain Peptides

A

Leu-, Met-Enkephalin
Substance P
Gastrin
Cholecystakinin
Vasoactive intestinal polypeptide
Insulin
Glucagon
Neurotensin

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12
Q

Neuropeptide Transmitters - list the Growth Factors

A

Nerve growth factor
Brain-derived neurotropic factor

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13
Q

Neuropeptide Transmitters - others

A

bradykinin
Angiotensin II
Calcitonin

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14
Q

Steps in Neurochemical Transmission (know this down cold)

A
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15
Q

Acetylcholine

A
  • First neurotransmitter discovered
  • Released by all preganglionic neurons of autonomic nervous system and postganglionic parasympathetic neurons
  • Released at neuromuscular junction
  • Many brain pathways
  • Many pharmacological agents interact with acetylcholine receptors
  • Role in cognitive function
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16
Q

Acetylcholine synthesis

A
  • Precursors
    -Acetyl-CoA from Kreb cycle activity
    -Choline from the diet β†’ lecithin is a good dietary source of choline
  • Primary synthetic Enzyme
    -choline acetyltransferase
  • Rate-limiting step of synthesis is Choline uptake into the presynaptic terminal
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17
Q

Presynaptic Cholinergic Neuron

A

functions in storage and release of neurotransmitters
* Storage
-Vesicular acetylcholine transporter (VAT)
-active transport
-counter ions (ATP)
* Release
-Involves vesicle docking and fusion with cell membrane
-calcium dependent
-Botulinum toxin sensitive→specific presynaptic ganglioside

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18
Q

Acetylcholine inactivation

A
  • Acetylcholinesterase (AChE)
    – Bound to post-synaptic membrane
    – Mediates hydrolysis of acetylcholine to choline and acetate
    – High catalytic activity
    – Primary target of nerve gas agents and organophosphate pesticides (they inhibit AChE)
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19
Q

Acetylcholine Receptors

A
  • Nicotinic
    – Ligand-gated cation channels
    – Heterologous pentamers
    β†’ Subunit families: ⍺1-⍺10, Ξ²2-Ξ²5, Delta, Epsilon, Gamma
    – Neuromuscular junction
    β†’ Subtype N1 (Nm)
    – Autonomic ganglia, adrenal medulla and brain
    β†’ N2 (N_N) subtype
  • Muscarinic
    – G-protein-linked
    – Single subunit or dimer of two subunits
    – Subtypes: M1-M5
    – Peripheral end-organs innervated by the parasympathetic nervous system
    – Wide distribution in the brain
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20
Q

Central Cholinergic Pathways

A
  • Basal forebrain to cortex and cingulate gyrus
    – Cognition, attention
    – Dementia therapy
  • Septo-hippocampal
    – Memory
    – Dementia therapy
  • Brainstem projections
    – Autonomic functions
  • Striatal interneurons
    – Motor system
    – Extrapyramidal
    – Parkinson’s therapy
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21
Q

GABA (Gamma - Aminobutyric Acid)

A
  • The primary inhibitory transmitter in the nervous system
  • Inhibitory electrophysiological effects are produced by increasing membrane chloride influx through GABA-A receptors
  • Along with glutamate (which is excitatory), it regulates the overall tone of nervous system activity
  • It is implicated in etiology of many brain diseases including Huntington disease, epilepsy, alcoholism, depression
  • Mediates the effects of most central nervous system depressant drugs
22
Q

GABA Synthesis

A
  • Kreb cycle shunt pathway
  • Precursor
    – Glutamate
  • Rate-limiting enzyme
    – Glutamic acid decarboxylase (GAD)
  • GAD isoforms
    – GAD65, GAD67
  • Enzyme co-factor
    – Pyridoxal phosphate (vitamin B6)
    – B6 deficiency may present with seizures
23
Q

GABA Storage and Release

A
  • Storage
    – Active transport into synaptic vesicles
    – Vesicular GABA transporter (VGAT)
  • Release
    – Vesicular, calcium-dependent
    – Non-vesicular, calcium-independent
    β†’ Involves reversal of presynaptic uptake protein function
24
Q

GABA Inactivation

A
  • Reuptake by presynaptic neuronal transporters
    – Re-packaged in synaptic vesicles
  • Reuptake by glial transporters
    – Enzymatic degradation
    – Several key metabolic enzymes involved
25
GABA Metabolism
* **Enzymatic degradation** – **GABA Transaminase (GABA-T)** * Converts GABA to succinic semi-aldehyde (SSA) * SSA converted to succinate by SSA dehydrogenase
26
GABA Receptors
* **GABA-A** – **Ligand-gated chloride channel** – Heterologous pentamer – Subunit families * a1-6, b1-4, g1-4, d1-2, t1, e1, r1-3 – Mediates β€œfast” inhibitory transmission (millisecond time course) * **GABA-B** – **G-protein-linked** – Heterologous dimer * GABR1, GABR2 – Mediates β€œslow” inhibitory transmission – Variably long time course
27
GABA-A Receptor Function
* GABA-A activation causes **neuronal inhibition** – Depresses activity of the CNS * Agonists are used for – Insomnia – Anxiety – Epilepsy – General anesthesia
28
Major GABA Pathways
* **Projection pathways** – Hippocampus β†’ Basket cells, stellate cells – Cerebellum β†’ Purkinje cells, Golgi cells – Striatonigral, pallidonigral β†’ Neurons in striatum and globus pallidus project to substantia nigra (Huntington disease) – Thalamocortical β†’ Thalamic nuclei project to neocortex (Absence epilepsy) * **Interneurons** – **Ubiquitous** including neocortex, basal ganglia, cerebellum, spinal cord
29
Glutamate
* The **primary excitatory transmitter** in the nervous system * Excitatory electrophysiological effects via **increased cation conductance** through activated **glutamate receptors** * Along with GABA (which is inhibitory), it regulates the overall tone of nervous system activity * Glutamate and related excitatory amino acids (EAAs) implicated in etiology of many neurological and psychiatric diseases including schizophrenia, epilepsy, stroke and neurodegenerative illnesses * Small but growing number of clinically relevant pharmacologic agents target glutamatergic neurons
30
Glutamate Synthesis
* Aminotransferase – Expressed in all cells * Krebs cycle enzyme – Uses vitamin B6 as co-factor * Glutamine synthetase – Expressed only in glia – Uses ATP as a co-factor * Glutaminase – Expressed only in neurons
31
Glutamate Neurochemistry
32
Glutamate Receptors
33
Glutamate Receptor Function
34
Major Glutamate Pathways
35
Brain Monoamines
36
Catecholamine Synthesis
37
Catecholamine Neurochemistry
38
Dopamine Receptors
39
Major Dopamine Pathways
40
Major Dopamine Functions
41
Norepinephrine Receptors
42
Major Norepinephrine Pathways
43
Major Norepinephrine Functions
44
Serotonin Neurochemistry
45
Serotonin Receptors
46
Major Serotonin Pathways
47
Major Serotonin Functions
48
Endogenous Opioid Neuropeptides
49
Major Opioid Receptors
50
Neurotransmitter Colocalization
51
Neurotransmitter Colocalization
52
Neurotransmitters summary

Neuropsych (15 decks)

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