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Psych 421: The Neural Basis of Behavior > Week 5: Neurotransmitter Synthesis and Pathways > Flashcards

Week 5: Neurotransmitter Synthesis and Pathways Flashcards

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1
Q

Classes of Neurotransmitter

A
  1. Acetylcholine (ACh)
  2. the Biogenic Amines
  3. the Amino Acids
  4. Neuroactive Peptides
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2
Q

Biogenic Amines

A
  1. Dopamine (DA)
  2. Norepinephrine (NE)
  3. Sertonin (5HT)
  4. Histamine
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3
Q

Amino Acids

A
  1. GABA
  2. Glutamate
  3. Glycine
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4
Q

Neuroactive Peptide Families

A
  1. Pro-opio-melanocortin (POMC) - contains beta-endorphin
  2. pro-enkephalin - contains met- and leu-enkephalins
  3. pro-dynorphin - contains dynorphin
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5
Q

4 criteria for calling a substance a neurotransmitter

A
  1. It must be synthesized in the neuron
  2. It must be released in sufficient amounts upon an AP to yield PSPs
  3. exogenous applications will mimic normal activity
  4. there must be some deactivating mechanism(s)
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6
Q

Dale’s Law

A

a mature neuron makes use of the name neurotransmitter in all of its synapses (original)

NEW: A mature neuron makes sure of the same combination of neurotransmitter substances in all of its synapses

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7
Q

Coexistance

A

the use of more than one transmitter by a neuron

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8
Q

Where does neurotransmitters synthesis occur?

A

All NT except neuroactive peptides: at the pre-synaptic terminal

Neuroactive Peptides: The nucleus

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9
Q

Synthesis of ACh

A

Acetyl Co-enzyme A + Choline –> Choline Acetyal Transferase (CAT) –> Acetylcholine (ACh)

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10
Q

Deactivating mechanism for ACh

A

Acetylcholinesterase (AChE)

Exists in the synapse next to the ACh receptor and exits in the terminal and on the presynaptic side of the synapse (which will break up any not-bound ACh)

The choline is recycled by a transporter on the external face of the synaptic cleft.

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11
Q

Critical Issues about vesicles

A
  1. they are essentially safety zones, they prevent NT from being broken down
  2. they are not saturated (not normally filled to capacity)
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12
Q

Vesicle Transporters: Proton Pumpers

A

Purpose: to keep the inside of the vesicle supplied with proteins

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13
Q

Vesicle transporters

A

exchange 2 protons for every molecule of NT

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14
Q

Types of Vesicle Transporters

A
  1. one for ACh
  2. One for biogenic amines (VMAT)
  3. One for glutamate
  4. One for GABA
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15
Q

Monoamine Neurotransmitters

A
  1. Catecholamines
    - Dopamina (DA)
    - Norepinephrine (NE)
  2. Indoleamines
    - Serotonin (5HT)
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16
Q

Dopamine Synthesis Pathway

A

Tyrosine –> L-DOPA (via tyrosine hydoxylase) –> Dopamine (via dopa decarboxylase)

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17
Q

Rate Limiting Enzyme for Catecholamines

A

tyrosine hydroxylase exists in an inactive form and needs pteridine-H4 cofactor to become active

Pteridine-H4 then becomes pteridine-H2 and pteridine reductase will then add H back to pteridine to make it active and able to activate tyrosine hydroxylase again

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18
Q

Synthesis pathway of Norepinephrine

A

tyrosine –> L-Dopa (via tyrosine hydroxylase) –> Dopamina (via dopa decarboxylase) –> Norepinephrine (via dopamine beta hydroxylase)

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19
Q

Deactivating Mechanism for Monoamines

A

Re-uptake - the drawing of NT molecules back into the pre-synaptic membrane via membrane transporters

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20
Q

General classes of membrane transporters

A
  1. Ones Glutamate

2. Ones for GABA, glycine, norepinephrine (NET), dopamine (DAT), serotonin (SERT), and choline

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21
Q

Similarities of general classes of membrane transporters

A
  1. they are both driven by the Na+ concentration gradient

2. they both co-transport another ion

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22
Q

Dissimilarities of general classes of membrane transporters

A
  1. the glutamate transporter is made up of a protein that spans the membrane 6-8 times; the others span the membrane 12 times
  2. Glutamate transporter requires the co-transport of K+; the others require the co-transport of Cl-
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23
Q

Enzymes that break down Catecholemines

A
  1. Monoamine oxidase (MAO)
  2. Catechol-o-methyl-transferase (COMT)

Both exist in the terminal and on the pre-synaptic side (where they break down free NT)

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24
Q

Short term feedback systems of catecholamines

A
  1. end product inhibition (inhibition)

2. Ca++ feedback (excitation)

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25
End Product Inhibition
accumulating amounts of DA in the presynaptic terminals will decrease the activity of tyrosine hydroxylase by converting pterdine-H4 to pterdine-H2
26
Ca++ feedback
the accumulation of Ca++ will directly (bind and make more efficient) and indirectly (GProtein systems) accelerate the activity of tyrosine hydroxylase
27
Induction
a long term feedback system for tyrosine hydroxylase the continued firing of a neuron may cuase that neuron's nucleus to produce more tyrosine hydroxlyase Likely accomplished by autoreceptors
28
Autoreceptor process for induction
prolonged release of NT results in prolonged stimulation of autoreceptors. the prolonged cAMP stimulation leads to the activation of CREB (a transcriptional activator protein) which when activated, it will cause the portion of genetic code produce more tyrosine hydroxylase Slow process
29
Synthesis of Serotonin
tryptophan --> 5HTP (via trytophan hydroxylase) --> 5HT (via 5HTP decarboxylase)
30
rate limiter enzyme of 5HT
availability of tryptophan | trytophan hydroxylase
31
Deactivating enzyme
MAO
32
Histamine synthesis
histadine --> histamine (via aromatic amino acid decarboxylase)
33
Histamine deactivation
reuptake by glial cells | no recycling
34
Glutamate sources
1. a product of the Krebs cycle in the neuron 2. neighboring glial cells supply glutamate neurons will convert glutamine into glutamate by glutaminase
35
Gluetamate deactivating system
reuptake by neuron and glial cells In glial cells, glutamate is converted to glutamine and then given back to the neurons
36
GABA synthesis
glutamate --> GABA (via glutamate acid decarboxylase (GAD))
37
How do Neuroactive Peptides differ from other NT
1. synthesis occurs in the nucleus 2. the type of vesicles that carry them 3. their method of exocytosis
38
Vesicles that hold Neuroactive peptide
Are "dense core" vesicles They lack proteins for herding into the active zones (so they can release anywhere along the membrane in the axon terminal) and for recycling (so only used once)
39
How do dense core vesicles release
they release anywhere on the axon terminal they require high level of Ca++ -- so long and intense stimulation of the neuron is required
40
Unconvention NT
NO (nitric oxide) | CGMP
41
NO Synthesis
L-arginine --> Nitric oxide and citulline (Via nitric oxide synthase) Neural stimulation will elicit the phasic release of NO
42
What does NO do?
NO stimulates guanylate cyclase to produce more cGMP It modfies the metabolism and release of transmitter on the presynaptic side
43
NO is tranfered
not by vesicles, and is not dependent on Ca++. It freely diffuses across membranes
44
Where is NO localized?
cortical interneurons, hippocampal cells, striatal interneurons, in cholinergic projection neurons in the pons
45
Types of Endogenous Cannabinoids
1. anadamide 2. 2DG Not stored, rapidly synthesized in response to depolarization and consequent to Ca++
46
Locations of CB1 receptors
high levels in hippocampus, cortex, cerebellum, and basal ganglia
47
Endocanabaniods regulate
GABA, they inhibit GABA
48
Process for endocanabaniods
DSI is initiated by depolarization, opening the N-type Ca++ channels Ca++ started the rapid production of endocanabiniods which then diffuse and bind to CB1 receptors and inhibit GABA
49
Monoamine Pathway
Catecholine Nuclei A1 - A13
50
Norepinephrine Pathway
A1 - A4 in Myel-enchephalon A5 - A7 in Met-enchaphalon *A6 locus coeruleus (met-encephalon)
51
Locus Coeruleus projects to
1. "dorsal tegmental bundle" | 2. central tegmental bundle
52
Dorsal tegmental bundle projects to
hypothalamus, septum, amygdala, olfactory bulb, hippocampus, cerebral cortex, central gray, cerebellum, recticular formation (Major limbic structures, major emotional processing centers) *** System is UNCROSSED
53
Dopamine Pathway
Projects to major limbic systems A8-A10 in the mes-encephalon A11-A13 in the di-encephalon Nucleus Accumbens
54
Serotonin Pathways
Raphe nuclei
55
ACh Pathways
1. stiatal interneurons 2. septo-hippocampal pathway 3. habelulo-interpendicular pathways 2. nucleus basalis to the frontal cortex
56
Glutamate pathways
1. entorhinal cortex to hippocampus 2, cerebral cortex to basal ganglia 3. hippocampus to septal area 4. granule cells in cerebellum
57
GABA Pathways
1. interneurons in CNS 2. Purkinje cell in cerebellum 3. basal ganglia to substantia nigra 4. basal ganglia to habenula
58
Endorphin pathways
hypothalamus
59
Enkephalin pathways
almost everywhere in CNS, no projection neurons use enkephalins
60
Histamine pathways
Not well defined,
61
endocanabinoid pathways
no pathways, but distributions are important

Psych 421: The Neural Basis of Behavior (6 decks)

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