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Neurobiology > Chapter 6 > Flashcards

Chapter 6 Flashcards

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1
Q

What are the common requirements to be labeled a neurotransmitter?

A
  • present in presynaptic neuron
  • released during synaptic activity
  • postsynaptic receptors
  • mechanism for inactivation
  • exogenous mechanism mimics endogenous release
  • blocked by antagonists
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2
Q

What is the general distinction between neurotransmitters and neuromodulators?

A

Based on effects of the molecule. Neuromodulators don’t directly cause electrical signals.

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3
Q

How do neuromodulators function?

A

They modulate synaptic transmission by altering neurotransmitter synthesis/release, modifying receptors or intracellular signaling paths, and modifying resting membrane potential.

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4
Q

What is the signaling speed of neuromodulators compared to neurotransmitters?

A

Neuromodulators generally have slower, more diffuse signaling.

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5
Q

What are the categories of neurotransmitters?

A

Small molecules (monoamines), neuropeptides, and nontraditional (unconventional) neuromodulators.

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6
Q

Where are small molecule neurotransmitters produced? How fast is the signaling?

A

Synthesized at the axon terminal, they provide faster signaling than neuropeptides.

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7
Q

What are examples of small molecule neurotransmitters?

A

ACh, amino acids, biogenic amines/monoamines, and purines.

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8
Q

How are neuropeptides synthesized?

A

They are synthesized in the cell body and transported anterogradely.

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9
Q

What are examples of unconventional neuromodulators?

A

Endocannabinoids and nitric oxide.

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10
Q

What are ionotropic receptors?

A

They provide faster signaling and are less selective than voltage-gated channels.

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11
Q

What is the structure of ionotropic receptors?

A

Composed of 3-5 subunits, grouped into classes based on common structures and pharmacological responses.

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12
Q

What are metabotropic receptors?

A

G-protein coupled receptors that initiate intracellular signaling cascades; slower response

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13
Q

What are the functional classifications of metabotropic receptors?

Gs, Gi, Gq

A

Gs activates adenylyl cyclase, Gi inhibits adenylate cyclase, and Gq activates phospholipase C.

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14
Q

What is acetylcholine (ACh)?

And where is it produced?

A

A neurotransmitter synthesized in specific neuron cell bodies.

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15
Q

What condition is associated with ACh?

A

Myasthenia gravis

Autoimmune disorder in which antibodies destroy the communication between nerves and muscle, resulting in weakness of the skeletal muscles

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16
Q

What special characteristics does NMDA have?

A

Magnesium block and glycine co-agonist.

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17
Q

What are the receptor types for GABA?

A

GABA-A receptors with specific permeability.

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18
Q

Where is dopamine released from?

A

Substantia Niagra pars compacta (SN) and Ventral tegmental area

Both midbrain regions

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19
Q

Where is the cell body distribution for norepinephrine?

A

Locus Coeruleus

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20
Q

What are the basic signaling paths for adrenergic receptors?

a1, a2, B1, and B2

A
  • Alpha-1 increases intracellular calcium
  • Alpha-2 inhibits adenylate cyclase
  • Beta-1/Beta-2 activate adenylte cyclase
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21
Q

What is the receptor affinity for norepinephrine and epinephrine?

A

Alpha-1 has greater affinity for norepinephrine than epinephrine.

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22
Q

Where are serotonin-synthesizing/distributing neurons located?

A

Raphe nuclei

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23
Q

Where are histamine-synthesizing neurons located?

A

Tuberomammillary nucleus of hypothalamus

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24
Q

What role does ATP play in neurotransmission?

A

All secretory vesicles contain ATP, but it is not always a neurotransmitter/neuromodulator.

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25
What are the types of adenosine receptors?
A1, A2x, and A3 (non-neuronal) ## Footnote All G protein receptors
26
How are neuropeptides synthesized?
prepropeptide -> endoplasmic reticulum -> propeptide + enzymes -> golgi apparatus -> vesicles -> anterograde axoplasmic transport ## Footnote This is all in the soma
27
What is the mechanism of action for endocannabinoids?
They inhibit GABA release from presynaptic cells.
28
What is nitric oxide's role in neurotransmission?
It diffuses out of the cell and activates soluble guanylyl cyclase (GTP) in the cytoplasm.
29
What are the hypothesized functions of nitric oxide in the nervous system?
Plasticity and neurodegenerative diseases.
30
What blocks nicotinic receptors at the neuromuscular junction?
alpha bungarotoxin ## Footnote However, this will not block postganglionic neurons
31
How is ACh synthesized?
- Acetyl CoA from glucose - choline from plasma - choline acetyltransferase (ChAT)
32
Where is a major source of ACh?
basal forebrain
33
What deactivates acetylcholinesterase (AChE)?
organophosphates ## Footnote Such as sarin and insectisides
34
Ionotropic effects of ACh
- excitatory: Na+ and K+ - neuromuscular junction at skeletal muscle - ganglia of visceral motor system - CNS
35
Metabotropic effects of ACh?
- parasympathetic postganglionic neurons - CNS
36
What is the ionotropic ACh receptor? What is unique about it?
Nicotinic receptors (nAChR); requires 2 ACh molecules to activate
37
Muscarinic receptors (mAChR)
- ACh agonist - from poisonous mushroom
38
Atropine
ACh antagonist; pupil dilation
39
Scopolamine
ACh antagonist; prevents motion sickness
40
Ipratropium
ACh antagonist; asthma treatment
41
How is glutamate synthesized?
glutamine taken up from plasma and converted in the mitochondria by glutaminase
42
What deactivates glutamate?
- reuptake in the presynaptic terminal - glia (glutamine synthesis converts back to glutamine)
43
Ionotropic effects of glutamate
excitatory in vertebrates
44
Metabotropic effects of glutamate
excitatory or inhibitory ## Footnote GluR 1 is excitatory, 2 and 3 inhibitory
45
What are the ionotropic glutamate receptors?
AMPA, NMDA, and Kainate ## Footnote all agonists
46
What are AMPA, NMDA, and Kainate permeable to?
Na+ and K+ ## Footnote NMDA also permeable to Ca2+
47
What are the different current patterns of glutamate ionotropic receptors? ## Footnote Hint: Think of graphs
- AMPA: sharp, fast - NMDA: slower - Kainate: slower inward current and longer to die out
48
How are NMDA receptors unique?
- involves Mg2+ blocking the pore until it is depolarized - glycine co-agonist
49
How are Kainate receptors unique?
Autoreceptors
50
Effect of glutamate metabotropic receptors (mGluR) in CNS and PNS?
CNS: cognitive processes PNS: vision
51
How is GABA synthesized?
glucose to glutamate during the TCA, and then glutamic acid to GABA via glutamic acid decarboxylase (GAD) ## Footnote GAD requires cofactor vitamin B6
52
How is GABA inactivated?
- reuptake neurons and glia by GAT - enzymatic breakdown into succinate and Y hydroxybutyrate ## Footnote hydroxybutyrate is the date rape drug
53
Are projection neurons mainly excitatory or inhibitory?
Excitatory
54
What is the ionotropic GABA A receptor permeable to?
Cl-
55
Benzodiazepine
GABA agonist; calming effect
55
Zolpidem
GABA agonist; sedative that treats insomnia
56
Ketamine
GABA agonist; anesthetic and treats depression
57
Alcohol (ethanol)
GABA agonist; depressant
58
What do barbituates do?
enhance GABA signaling; anesthesia and epilepsy
59
Function of metabotropic GABA B receptors
- inhibits adenylyl cyclase - activates inward K+ current - blocks Ca2+ channels
60
How is glycine synthesized?
serine precursor; serine hydroxylase methyltransferase
61
How is glycine inactivated?
Glycine specific Na+ cotransporter ## Footnote by recycling
62
Is glycine inhibitory or excitatory? Where are these synapses?
inhibitory; spinal cord
63
What ion are ionotropic glycine receptors permeable to?
Cl-
64
Strychnine
Glycine competitive antagonist
65
66
What is GABA?
GABA (Gamma-Aminobutyric Acid) is a neurotransmitter that inhibits neuronal activity.
67
What are the receptor types for GABA?
GABA-A (ionotropic, ligand-gated Cl⁻ channels).
68
What is the permeability of GABA-A receptors?
Allows Cl⁻ ions to flow into the cell, causing hyperpolarization.
69
How is GABA synthesized?
Synthesized from glutamate by the enzyme GAD (glutamate decarboxylase).
70
How is GABA reuptaken?
Reuptake via GABA transporters (GAT).
71
How is GABA degraded?
Degraded by GABA transaminase to succinic semialdehyde, which is further metabolized.
72
Where is dopamine synthesized?
Synthesis Location: Substantia nigra, ventral tegmental area (VTA).
73
What are the projection areas for dopamine?
Caudate, putamen, prefrontal cortex, nucleus accumbens.
74
What are the receptor types for dopamine?
D1, D2, D3, D4, D5 (all are GPCRs).
75
How is dopamine synthesized?
Synthesized from tyrosine via tyrosine hydroxylase → L-DOPA → dopamine.
76
How is dopamine reuptaken?
Reuptake by dopamine transporters (DAT).
77
How is dopamine degraded?
Degraded by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT).
78
Where is norepinephrine synthesized?
Synthesis Location: Locus coeruleus (LC).
79
What are the projection areas for norepinephrine?
Cortex, hippocampus, spinal cord.
80
What are the receptor types for norepinephrine?
Alpha-1, Alpha-2, Beta-1, Beta-2 (all GPCRs).
81
How is norepinephrine synthesized?
Synthesized from dopamine via dopamine beta-hydroxylase.
82
How is norepinephrine reuptaken?
Reuptake by norepinephrine transporters (NET).
83
How is norepinephrine degraded?
Degraded by MAO and COMT.
84
Where is epinephrine synthesized/distributed from?
Medullary epinephrine neurons
85
What is the role of epinephrine?
Fight-or-flight response.
86
What are the receptor types for epinephrine?
Alpha-1, Alpha-2, Beta-1, Beta-2 (all GPCRs).
87
How is epinephrine synthesized?
Synthesized from norepinephrine by the enzyme phenylethanolamine-N-methyltransferase (PNMT).
88
How is epinephrine reuptaken?
Reuptake by norepinephrine transporters (NET), although less prominent than in norepinephrine.
89
How is epinephrine degraded?
Degraded by MAO and COMT.
90
What is the role of ATP in neurotransmission?
Present in all synaptic vesicles but is not always the primary neurotransmitter. It acts as a neuromodulator through P2X receptors (ionotropic).
91
How is ATP synthesized?
Synthesized in the mitochondria from ADP or AMP.
92
How is ATP reuptaken?
Reuptake by P2Y and P2X receptors.
93
How is ATP degraded?
Degraded by ectonucleotidases to adenosine.
94
What are P2X receptors?
Ionotropic receptors activated by ATP.
95
What is the function of P2X receptors?
Allow cation influx (Na⁺, Ca²⁺), which causes depolarization.
96
How is ATP reuptaken via P2X receptors?
ATP is cleaved into ADP and AMP by ectonucleotidases.
97
How are ADP and AMP degraded?
ADP and AMP can be further broken down to adenosine, which is removed via nucleoside transporters.
98
What are the receptor types for adenosine?
A1, A2A, A2B, A3 (all GPCRs).
99
How is adenosine synthesized?
Derived from ATP through ectonucleotidase activity (hydrolysis of ATP to adenosine).
100
How is adenosine reuptaken?
Reuptake via equilibrative nucleoside transporters (ENTs).
101
How is adenosine degraded?
Degraded by adenosine deaminase (ADA) to inosine.
102
How are neuropeptides synthesized?
Synthesized as larger precursor proteins that are cleaved into active peptides (e.g., pro-opiomelanocortin → ACTH, beta-endorphins).
103
What are the receptor types for neuropeptides?
Always metabotropic receptors (GPCRs).
104
How is neuropeptide reuptake characterized?
Typically, reuptake is not significant. Neuropeptides are often degraded locally.
105
How are neuropeptides degraded?
Degraded by peptidases and other proteolytic enzymes.
106
What are the major types of endocannabinoids?
Anandamide, 2-AG (2-arachidonoylglycerol).
107
How are endocannabinoids synthesized?
Synthesized on demand from membrane lipids (e.g., phospholipids) in response to Ca²⁺.
108
What are the receptor types for endocannabinoids?
CB1 (central nervous system), CB2 (peripheral immune system) - both GPCRs.
109
What is the mechanism of endocannabinoids?
Retrograde signaling; they inhibit presynaptic neurotransmitter release (e.g., GABA, glutamate).
110
How is anandamide reuptaken?
Anandamide is reuptaken via fatty acid amide hydrolase (FAAH).
111
How are endocannabinoids degraded?
Degraded by FAAH (for anandamide) and monoacylglycerol lipase (MAGL) (for 2-AG).
112
How is nitric oxide synthesized?
Synthesized from L-arginine by nitric oxide synthase (NOS), activated by Ca²⁺-calmodulin.
113
What is the mechanism of nitric oxide?
Diffuses out of the cell, activates soluble guanylyl cyclase (SGC) in the cytoplasm, producing cGMP.
114
How is nitric oxide reuptaken?
No reuptake since NO is a gas and diffuses freely.
115
How is nitric oxide degraded?
Spontaneous oxidation, inactivation via reactive nitrogen species.
116
What are the types of adrenergic receptors?
- Alpha-1: Increases intracellular calcium. - Alpha-2: inhibits adenylate cyclase - Beta-1/Beta-2: activate adenylate cyclase
117
Where are norepinephrine and epinephrine synthesized?
Norepinephrine is synthesized in the locus coeruleus and epinephrine in the adrenal medulla.
118
How are norepinephrine and epinephrine reuptaken?
Both norepinephrine and epinephrine are primarily recycled via the norepinephrine transporter (NET).
119
How are norepinephrine and epinephrine degraded?
MAO and COMT are responsible for the breakdown.
120
What does the neuropeptide Substance P do?
pain and temperature perception
121
What does the neuropeptide Y do?
feeding behavior
122
What does D-1 type dopamine receptor do?
Acivate adenylate cyclase (Gs)
123
What does D-2 type dopamine receptor do?
Inactivate adenylate cyclase (Gi)
124
What is a function of dopamine?
Stimulates vomiting
125
Is Parkinson's associated with a loss or increase of dopamine?
Loss
126
What can lead to cataplexy (sudden muscle weakness)? ## Footnote Hint: related to dopamine
Dopamine agonists
127
Propanolol
B receptor antagonist (norepinephrine and epinephrine) used for migranes

Neurobiology (10 decks)

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