CNS Neurotransmission - Craviso Flashcards
1
Q
What determines the type of activity that a neuron uses/
A
the ratio of excitatory to inhibitory inputs to that neuron
2
Q
What small molecule controls sleep, arousal, mood, and appetite?
A
serotonin
3
Q
What small molecule controls mood, arousal, and appetite
A
NorEpi
4
Q
What small molecule controls movement (motor control), behavior, mood, and perception?
A
Dopamine
5
Q
What small molecule controls arousal, and cognition (memory and learning)
A
ACh
6
Q
What small molecule controls wakefulness and equilibrium?
A
histamine
7
Q
What is the excitatory amino acid in the CNS?
A
glutamic acid
8
Q
What is the inhibitory amino acid in the CNS?
A
GABA
9
Q
methionine, leucine enkephalin, and substance P are all involved in (blank) transmission
A
pain
10
Q
methionine, leucine enkephalin, and substance P are what class of molecule?
A
neuropeptides
11
Q
T/F: neuropeptides are also found in the periphery
A
true
12
Q
What are the function of the endocannabinoids?
A
memory, cognition, and pain perception
13
Q
Anandamide and 2-AG are what class of molecule?
A
endocannabinoid
14
Q
Pain transmission uses (hierarchical/non-hierarchical) transmission
A
hierarchical
15
Q
Primary sensory and motor pathways uses (hierarchical/non-hierarchical) transmission
A
hierarchical
16
Q
In non-hierarchical projecting, neurons from a single anatomical location extend multiple divergent connectoins to target cells (within/outside) the region in which the neuron originates
A
outside
17
Q
The raphe nucleus produces what substance?
A
serotonin
18
Q
Because the raphe nucleus produces serotonin, projections from the raphe nucleus are associated with what activities?
A
sleep, arousal, and mood behavioral changes hallucinations feeding behavior vomiting (5HT3 ionotropic receptors in area postrema)
19
Q
NorEpi is produced in what area of the brain/
A
locus ceruleus
20
Q
Because NorEpi is produced in the locus ceruleus, projections from there would be associated with what types of behavior?
A
Arousal and mood
appetite
cardio control
21
Q
Dopamine neurons project from what three brain structures?
A
midbrain
striatum
hypothalamus
22
Q
The mesocortical pathway is involved in what functions?
A
mood and behavior
23
Q
the nigrostriatal pathways are involved in what functions/
A
motor control
24
Q
the tuberoinfundibular pathway is involved in what function?
A
endocrine
25
What pathway is involved in prolactin secretion?
tuberoinfundibular pathway
26
Which ACh pathway is involved in motor control in concert with the dopamine systems?
mesopontine
27
Which ACh pathway is involved in arousal, learning, and memory?
basal forebrain pathway
28
ACh can have effects via muscarinic (GPCR/ionotropic) receptors as well as nicotinic (GPCR/ionotropic) receptors located PREsynaptically
muscarinic GPCR
| nicotinic ionotropic
29
Where do histamine projections arise in the brain?
tuberomammillary nucleus of the hypothalamus
30
Histamine works to help regulate equilibrium in what brain structure?
cerebellum
31
T/F: CNS methods of pre and post synaptic transmission are the same as the ones in the periphery
true
32
(Pre/post) synaptic modulation has effects on synthesis, storage, release, reuptake and/or degradation of neurotransmitters; agonist or antagonist activity at nerve terminal autoreceptors
presynaptic
33
(Pre/post) synaptic modulation acts as receptor agonist, antagonist or modulatory activity; degradation of neurotransmitters
post synaptic
34
What are the six major mechanisms of neurotransmitter modulation?
1. presynaptic
2. post synaptic
3. neurohormones
4. neuromodulators
5. effects on voltage gated ion channels
6. non-selective effects (anesthetics)
35
Metabotropic GPCRs are found mostly in the (CNS/periphery)
periphery
36
```
A and b adrenergic
dopamine receptor
muscarinic ACh
histamine
neuropeptide/endocannabionoid receptors
*most* 5HT receptors
glutamate and GABA receptors
```
these are all what class of receptors?
metabotropic GPCRs
37
Describe the process of activating a metabotropic GPCR?
1. neurotransmitter binds
2. G protein is activated
3. G protein subunit or second messengers modulate the ion channels
4. ion channel opens
5. ions flow across mebrane
38
What receptor class is found mostly at neuromuscular junctions?
ionotropic receptos (aka ligand-gated ion channels)
39
Describe how a ligand gated ion channel opens?
1. neurotransmitter binds
2. channel opens
3. ions flow across membrane
40
What types of ligand-gated ion channels DEPOLARIZE cells?
```
AMPA (Na)
Kainate (Na)
NMDA (Ca and Na)
certain glutamate receptors
Nicotinic ACh (Na and Ca)
5-HT3 (Na)
```
41
What types of ligand-gated ion channels HYPERPOLARIZE cells?
GABA-a (Cl-)
| Glycine (Cl-)
42
Excitatory neurotransmission in the CNS is balanced by feed (forward/reverse) and recurrent inhibitory actions of GABA
feed forward
43
Does inhibitory or excitatory neurotransmission dominate
inhibitory
44
T/F: inhibitory and excitatory neurotransmission is paired to a neuron
true
45
Over inhibition leads to....
coma
46
over stimulation leads to....
seizures
47
What mediates major excitatory inputs and inhibitory inputs to postsynaptic neurons in the CNS?
amino acid neurotransmitters
48
(blank) is synthesized from glutamate by glutamic acid decarboxylase
GABA
49
glutamic acid decarboxylase requires the cofactor (blank)
pyridoxal phosphate
50
GABA is metabolized by GABA-amino transferase found where in the cell and in what cell type?
in the mito of glial cells
51
What is the precursor to glutamate?
glucose
52
Is GABA synthesized in the pre or post synaptic cell?
presynaptic
53
what protein allows for GABA to be brought back into the presynaptic cell or into the glial cell?
GABA transporter GAT
54
what protein is responsible for the storage of GABA and glycine in neuronal vesicles?
VIATT
55
What is the most important type of GABA receptor?
GABA-a ionotropi
56
Is GABA a or GABA b metabotropic?
GABA-b
57
decrease in Ca conductance via GABA receptors leads to (depol/hyperpol) of the post synaptic cell
hyperpolarization
58
GABA uptake may (inc/dec) cAMP production
decrease/inhibit
59
GABA receptors that are coupled to activation of K channels produce what type of currents?
slow, inhibitory synaptic currents
60
GABA-a and GABA-c channels, when bound to GABA, allow the influx of what ion?
Cl-
61
GABA a and GABA c channels mediate (IPSPs/EPSPs)
IPSPs
62
T/F: GABA signaling can mediate IP3 production
true
63
PRE-synaptic GABA-b receptors (inc/dec) the release of GABA into the cleft, having what effect?
decreases GABA, therefore less inhibition
64
In what part of the CNS do we see a high concentration of GABA b receptors?
spinal cord
65
Baclofen (Lioresal) is a GABA (a/b) agonist that is used for muscle spasticity in ALS
GABAb
66
T/F: GABA uptake by the GABAb receptors on adjacent presynaptic terminals can also inhibit glutamate release
true
67
the majority of GABA's effects are mediated by which GABA receptor?
GABA a
68
GABA (hyperpol's/depol's) cells and generates IPSPs
hyperpolarizes
69
What drugs can act on the GABA a channel?
barbiturates
| steroids
70
WHat are the two types of GABA transmission?
phasic and tonic inhibition
71
Describe tonic GABA inhibition?
continuous activation of extra-synaptic receptors (receptors that are on the nerve surface just not in the cleft) by ambient GABA
72
Describe phasic GABA inhibition?
GABA a Cl- channels open together and quickly in response to GABA vesicle emptying into the clef, then there is resolution in time and space
73
T/F: glycine channels are both ionotropic and metabotropic
FALSE, only ionotropic!!
74
what ion do the ionotropic glycine channels move?
Cl-
75
T/F: therapeutic agents against glycine channels have been found to be useful in MS
false; no therapeutic agents for glycine channels
76
What is the role of glycine in the spinal cord?
1. motor rhythm generation
2. coordination of reflex responses
3. processing of sensory signals
77
What are the two locations besides the spinal cord that glycine is used in the CNS?
brain stem and reticular formation
78
What part of rat poison is a glycine antagonist and power convulsant?
strychnine
79
T/F: there are Na dependent glycine transporters on both the presynaptic cell and glial cells
true
80
What is the precursor to glycine?
glucose to serine to glycine
81
What enzyme converts serine into glycine?
serine hydroxy methyltransferase
82
What enzyme packages glycine into vesicles?
VIATT
83
What cell is responsible for the majority of glutamate reuptake?
astrocytes
84
what is glutamate converted into in the astrocytes?
glutamine
85
what happens to the glutamine in the astroctyes?
it is pumped backed out and taken back up by the presynaptic neuron
86
what transporter allows glutamine back into the presynaptic neuron?
EATT
87
What converts glutamine into glutamate?
glutaminase
88
What enzyme packages glutamine into vesicles?
VGLUT
89
T/F: all three groups of mGluR are found pre and post synaptically and on astrocytes
true
90
Which group of mGluR augments the response?
group 1
91
which groups of mGluR decreases the response?
groups 2 and 3
92
NON-NMDA ionotropic GluR are broken down into what two types of receptors?
AMPA receptors
| Kainate receptors
93
What are the two major groups of ionotropic GluR?
NON-NMDA and NMDA
94
AMPA receptors primarily pump what ion?
Na
95
T/F: AMPA receptors can pump Ca as well as Na
true
96
What type of receptor mediates the majority of excitatory synapses?
AMPA
97
(AMPA/Kainate) receptors play a role in neural plasticity
AMPA
98
T/F: Kainate receptors primarily pump Ca
false; primarily pump Na but can also pump Ca
99
T/F: Kainate receptors are found pre and post synaptically
true
100
T/F: kainate receptors can play a role in neural plasticity
true
101
(NON-NMDA/NMDA) GluR primarily conduct Ca
NMDA
102
(NON-NMDA/NMDA) GluR are essential for neural plasticity and for long-term potentiation of synapse structure and funtion (aka learning and memory)
NMDA
103
NMDA receptors have EXTERNAL binding sites for what two excitatory transmitters?
glutamate and glycine
104
what is the role of glycine in NMDA glutamate receptors?
an essential co-agonist
105
At what membrane potential does Mg clog the NMDA pore?
-50mV
106
Describe the steps in long-term potentiation via the NMDA and AMPA costimulation?
1. Glutamate binds to NMDA, nothing happens
2. AMPA generally doesn’t let Ca in. BUT if you activate the NMDA receptor, you let Na in through the AMPA receptor
3. Cell depolarizes, Ca comes in through the NMDA receptor
4. Now you can do a shit ton with the Ca in the cell
107
after long term potentiation lets Ca into the post synaptic cell, what intracellular enzymes are activated?
1. Calmodulin Kinase II
| 2. Protein Kinase C
108
What is the result of intracellular enzyme activation in LTP?
substrate phosphorylation and increased insertion of AMPA channels into the membrane
109
What intracellular enzymes are activated in LDP?
protein phosphatases that dephosphorylate their substrates and cause internalization of AMPA receptors
110
What is the big picture reason for having LTP and LDP?
maintenance of neuronal networks and circuits
111
LTP increases the sensitivity to (blank) while LDP decreases the sensitivity to it
glutamate
112
Excessive activation of NMDA (blank) receptors causes excitotoxicity
glutamate
113
what disease states result in excessive NMDA activity?
ischemia, stroke, head injury, hypoglycemia, repeated intense seizures
114
What is the mechanism of toxicity of extra NMDA activation?
increased levels of Ca via voltage gated Ca channels that lead to over activation of cellular processes
115
(blank), either alone or with its superoxide free radicals, contributes to the cell death
NO
116
In NMDA toxicity, positive feedback of newly maded (blanks) act on the NMDA receptor
polyamines
117
Describe the steps in NMDA glutamate receptor excitotoxicity?
1. glutamate is released and activates the AMPA channel
2. Na flows in via AMPA
3. Depol from AMPA Na allows Mg to pop out of the NMDA receptor
4. Ca can flow in via VGCC
5. Ca in the cell activates a ton of shit including toxic NO production
6. Polyamines made by intracellular calcium further act on the NMDA receptor and make the problem even worse
