CNS Neurotransmission- Craviso Flashcards
1
Q
(blank) are the individual signaling elements of the brain
A
neurons
2
Q
An average neuron has (Blank) synaptic connections and receives even more
A
1000
3
Q
What is activity of the brain dependent on?
A
ratio of excitatory and inhibitory inputs to a neuron
4
Q
Whar are the small molecules neurotransmitters in the brain?
A
serotonin norepinephrine dopamine acetylcholine histamine
5
Q
What small molecule is this:
affects sleep, arousal, mood, appetite
A
serotonin
6
Q
What small molecule is this:
affects mood; arousal, appetite
A
norepinephrine (NE)
7
Q
What small molecule is this: affects movement (motor control); behavior, mood, perception
A
Dopamine (DM)
8
Q
What small molecule is this:
affects arousal, cognition (memory and learning)
A
Acetylcholine (ACh)
9
Q
What small molecule is this:
affects wakefulness, equilibrium
A
Histamine
10
Q
What are the amino acids (found primarily in the CNS)- that mediate major excitatory and inhbitiory neutrotransmision?
A
excitatory-glutamic acid (glutamate)
inhibitory- y-amino butyric acid (GABA) glycine
11
Q
What are the neuropeptide neutrotransmitters and what do they do?
A
methionine and leucine enkephaline -pain transmission
substance p- pain transmission
12
Q
What are the endocannabinoid neurotransmitters and what do they do?
A
memory, cognition, pain perception
- anandamide,
- 2-arachidonylglycerol (2-AG)
13
Q
Pain is transmitted in a highly sequential and interconnected way called (blank)
A
long-hierarchical
14
Q
What is this:
neurons from a single anatomical location extend multiple, divergent connections to target cells outside the region in which the neurons originate
A
non-hierarchical projections
15
Q
Serotonin (5-HT) neurons projected from the (Blank)
A
raphe nucleus
16
Q
What does this:
functions in sleep, arousal, mood, behavioral changes, hallucinations, feeding behaviors, vomiting
A
serotonin
17
Q
(blank) projects from the locus coeruleus
A
norepinephrine
18
Q
How do you treat spasticity in individuals with amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS)?
A
GABA analog called baclofen (Lioresal)
19
Q
How are the primary sensory and motor pathways transmitted?
A
in a long-hierarchical fashion (relay)
20
Q
What are the 2 pathways that serotonin (5-HT) is involved in?
A
- ascending raphe projections
- descending raphe projections
21
Q
What are the functional aspects of norepinephrine (NE)?
A
- arousal and mood
- appetite
- cardiovascular control
22
Q
What are the 2 pathways that norepinephrine (NE) participates in?
A
- locus coeruleus projections
- lateral tegmental projections
23
Q
(blank) neurons project from the midbrain, striatum and hypothalamus
A
Dopamine (DM)
24
Q
What are the functional aspects of dopamine?
A
- mood
- behavioral changes
- motor control
- neuroendocrine function (prolactin secretion)
- vomiting (area postrema)
25
What are the three pathways that dopamine participates in?
tuberinfudibular pathway
nigrostriatal pathway
mesocortical/mesolimbic pathways
26
What are the functional aspects of dopamine?
- mood
- behavioral changes
- motor control
- neuroendocrine function (prolactin secretion)
- vomiting (area postrema)
27
(blank) neurons project from the forebrain and brainstem
CHolinergic (Ach)
28
What are the functional aspects of cholinergic (Ach)?
- arousal
- learning and memory
- motor control (in concert with dopamine)
- effects via muscarinic (G-protein linked) receptors and via nicotinic (ionotropic) receptors located presynaptically
29
If Ach is having effects on muscarinic receptors what kind of receptor are they?
G-protein linked
30
If Ach is having effects on nicotinic receptors, what kind of receptors are they? Where are these receptors located?
ionotropic
| -presynaptically
31
What are the 2 pathways that acetycholine particpates in?
- basal forebrain pathways
| - mesopontine pathways
32
(blank) neurons project from the hypothalamus
Histamine
33
What are the functional aspects of histamine?
- Arousal and wakefulness
| - Equilibrium (cerebellum)
34
What is the pathway that histamine participates in?
-tuberomammillary nucleus of the hypothalamus
35
Pre-synaptically, how can you modulate the action of a neurotransmitter?
-mess with effects of synthesis, storage, release, reuptake and/or degredation of neurotransmitters; agonists or antagonist activity at nerve terminal autoreceptors
36
Post-synaptically, how can you modulate the action of a neurotransmitter?
-mess with receptor agonist, antagonist or modulatory activity; degredation of neurotransmitters
37
Whar are some other ways you can mess with neurotransmitters?
-mess with neurohormones, neuromodulators, effects on voltage-gated ion channels, non-selective effects (anesthetics)
38
How is acetylcholine primarily removed?
via degredation (via acetycholinesterase)
39
HOw are most neurotransmitters removed?
primarily by reuptake
40
What is another name for metabotropic receptors?
G-protein coupled receptors
41
What is the most common type of receptor OUTSIDE the cns?
metabotropic (G-protein coupled receptors)
42
Which have quicker responses, metabotropic (G-protein) or ionotropic?
ionotropic receptors
43
How long does it take for metabotropic (G-protein receptors) to respond and how long does the response last?
- Several HUNDREDS of milliseconds
| - for seconds and even minutes
44
What receptors are metabotropic receptors?
-All known alpha and beta adrenergic, dopamine, muscarinic ACh, histamine, neuropeptide, and endocannabinoid receptors
MOST 5-HT receptors
-metabotropic glutamate and GABA receptors
45
What is the only small molecule neurotransmitter that does not have a metabotropic receptor?
NE (norepinpehrine)
46
What is another name for ionotropic receptors?
Ligand-gated ion channels
47
Where do you find ionotropic receptors?
outside the CNS-predominantly neuromuscular junctions
48
How long does it take for an ionotropic receptor (ligand-gated ion channel) to respond and how long does the response last?
responses occur within a few milliseconds, lasts for only milliseconds
49
So which is faster and which lasts longer (ionotropic, metabotropic)
faster-ionotropic
| longer- metabotropic
50
What are the ionotropic receptors that depolarize cells?
Classes of glutamate receptors:
- AMPA (Na+)
- Kainate (Na+)
- NMDA (Ca2+ and Na+)
Nicotinic ACh receptors (Na+ and Ca2+)
5-Ht3 Receptors (Na+)
51
What are the ionotropic receptors that hyperpolarize cells?
GABA (Cl-) receptors
| glycine (Cl-) receptors
52
What is the predominate receptor in the brain?
Ionotropic receptors (ligand-gated ion channels)
53
So what kind of receptors do mucarinic acetycholine bind to?
| What kind of receptors does nicotinic acetycholine bind to?
metabotropic (Ms go together Muscarinic= Metabotropic)
| ionotropic (Ns go together Nictoinc =ioNotropic)
54
What is the ion associated with AMPA?
Na+
55
What is the ion associated with kainate?
Na+
56
What is the ion associated with NMDA?
Ca2+ and Na+
57
What is the ion associated with 5-HT3?
Na+
58
What is the ion associated with GABA a?
Cl-
59
What is the ion associated with nicotinic ACh receptors?
Na+ and Ca2+
60
What is the ion associated with glycine?
Cl-
61
Amino acid neurotransmitters mediate (blank) by glutamate (pre-synpatically/ post-synaptically).
major excitatory inputs
| post-synaptically
62
Amino acid neurotransmitters mediate (blank) by GABA (pre-synpatically/ post-synaptically).
major inhibitory inputs
| post-synaptically
63
How do you balance out excitatory transmission by amino acid neurotransmitters?
via feed-forward and recurrent inhibitory actions of GABA released from interneurons
64
Inputs to neurons paired to achieve a coordinated balance between excitatory (ESPS) and inhibitory (IPSP) events but (blank) neuro-transmission predominates
Inhibitory
65
What happens if you interfere with the ESPS/IPSP relationship?
highly disruptive- results in extremes such as comatose versus seizues
66
How do you make GABA?
synthesized from glutamate, by glutamic acid decarboxylase.
67
What does glutamic acid decarboxylase require to make GABA?
Pyridoxal phosphate
68
How is GABA metabolized?
By glial cells and mitochondria of neurons cuz they have GABA-amino transferase which metabolizes GABA
69
Where is GABA-amino transferase found?
in mitochondria of neurons and glial cells
70
A metabotropic receptor (GABA-B) in the nerve terminal can modulate the way GABA is released, does it increase GABA or decrease GABA release?
Decrease
71
Which is more important GABA-B or GABA-A?
GABA- A
72
Why do metabotropic GABA-B receptors inhibit GABA release?
- decreased Ca2+ conduction
- coupling to K+ channel which produces inhibitory signal
- regulating IP3 production and/or inhibit cAMP production
(i. e make it impossible for the GABA transporter to become stimulated enough to release GABA)
73
Presynatpic receptors (GABA -B) decreases release of (blank) and (blank).
GABA
| Glutamate
74
GABA b has a role in modulating the effects of GABA at (blank) receptors as well as the effects of other neurotra
GABA A
75
Where do you find a high concentration of GABA b receptors?
In spinal cord
76
What drug is a GABA B agonist that is used for treating spasticity (involuntary and abnormal muscle contractions) in individuals with Amyotrophic Lateral Sclerosis (ALS) and multiple sclerosis (MS)?
baclofen (Lioresal)
77
Majority of GABAs effects are mediated by (blank) receptors.
GABA A
78
GABA a receptors are (blank) conducting ion channels.
Cl-
79
GABA (blank) postsynaptic cells and generates IPSPs
Hyperpolarizes
80
Based on the location of GABA A receptors, there are 2 types of GABA neurotransmission... what are they?
Phasic and Tonic
81
How do you get tonic inhibition via GABA?
continuous activation of extra-synaptic receptors by ambient GABA
82
How do you get phasic inhibition via GABA?
Rapid, synchronous opening of channels in synaptic cleft; resolution in time and space
83
What kind of GABA receptors will cause tonic inhibition?
Extrasynaptic GABA A receptors
84
What kind of GABA receptors will cause phasic inhibition?
Synaptic GABA A receptor
85
Where do you see the majority of glycine acting?
in the spinal cord
| minor places-> brain stem, reticular formation
86
What does glycine do?
control motor rhythm generation, coordination of reflex responses and processing of sensory signals
87
What are the kinds of receptors that glycine utilizes?
Cl- conducting ion channels
| NO metabotropic receptors
88
What are the therapeutic agents that work on glycine channels?
there aren't any
89
What is an antagonist of glycine channels that are powerfu convulsants?
Strychnine (occurs in nature in certain seeds; an ingredient in rat poison)
90
After being released, glutamine reuptake occurs via tranporters present on (bank) and on (Blank).
Nerve terminals
| Astrocytes
91
What is responsible for the majority of glutamate reuptake?
astrocytes
92
What happens in the astrocyte to glutamate?
it is converted to glutamine for the nerve terminal to take it up to replenish the glutamate pool
93
What are the metabotropic receptors for glutamate?
there are three:
| -Group 1, Group 2, Group 3
94
What are the Group I metrabotropic receptors for glutamate (mGluR)?
mGluR receptors (augment responses)
95
What do Group II and Group III mGluR receptors do?
decrease response
96
Where do you find metabotropic receptors for glutamate?
pre and post synaptically and on astrocytes
97
What are the 2 major types of glutamate ionotropic receptors?
Non-NMDA receptors and NMDA receptors (N-methyl-D-aspartate)
98
What are the non-NMDA receptors?
AMPA receptors and Kainate receptors
99
What ions conduct through AMPA receptors?
primarily Na+
| some also permeable to Ca2+
100
What do AMPA receptors do?
mediate the majority of excitatory synapses
101
Do AMPA receptors play a major role in neural plasticity?
NOOO they play a minor role
102
What kind of ions do Kainate receptors conduct?
primarily Na+, some may also be permeable to Ca2+
103
Where do you find Kainate receptors?
Pre and Post-synaptically
104
What do Kainate receptors do?
play a role in neural plasticity
105
What kind of ions are conducted through a NMDA glutamate receptor?
Primarily Ca2+ and also conduct Na+
106
What do NMDA glutamate receptors do?
They mediate neural plasticity and change neuronal activity into long-term changes in synapes structure and function (i.e play a role in learning and memory)
107
NMDA glutamate receptors containe (blanK) binding sites for gluatamate and glycine (an essential co-agonist), and an (blank) binding site for Mg2+.
External
| Internal
108
At membrane potentials more negative than -50mv, what happens in NMDA glutamate receptors?
Mg2+ will go inside the channel, bind to the internal receptor and block the channel
109
Normal synaptic release of glutamate activates only (Blank) receptor channels
AMPA (or kainate)
110
So glutamate binds to AMPA receptor, then what happens?
sodium goes in and depolarizes cell.
111
So glutamate binds to AMPA receptors, sodium enters and you get a strong depolarization... then what happens?
glutamate and glucine will bind and kick out the Mg2+ to open the receptor and calcium then will enter which will cause neuroplasticity
112
So how do you activate NMDA receptors?
requires strong depolarization and simultaneous binding of 2 different agonists
113
(blank) receptors mediate neural plasticity
NMDA
114
What increases sensitivity of post-synaptic neurons to glutamate?
Long-term Potentiation (LTP)
115
What does LTP do to AMP receptors?
adds them to the post-synaptic terminal in the early phase which will result in changes in synpatic connections
116
What does Long term depression (LDP) do?
decreases sensitivity of post-synaptic neurons to glutamate
117
How does LDP affect AMPA receptors?
down regulates them -> causes internalization of those receptors
118
HOw does LDP work?
NMDA receptors let calcium and sodium in that activates protein phosphatases that dephosphorylate substrates and results in internalization of AMPA receptors
119
How does LTP work?
NMDA receptors let calcium and sodium in that activates protein kinase C and Ca, calmodulin kinase II which results in substrate phosphorylation and this insertion of AMPA receptors in post synpatic terminal
120
What receptors afffect your memory?
NMDA receptors
121
What is the overall significance of LTP and LDP?
maintenance of neuronal networks/circuits
122
What does excessive activation of NMDA glutamate receptors cause?
excitotoxicity
123
How can you get excitotoxicity from excessive activation of NMDA glutamate receptors?
can result from ischemia, stroke, head injury, hypoglycemia, repeated intense seizures
124
What is the mechanism behind excessive activation of NMDA glutamate receptors causing excitotoxicity?
due to large increases in neuronal cytosolic Ca2+ (through both NMDA receptors and Ca voltage gated ion channels) -> that overactivate a variety of cellular processes controlled by calcium
125
How does a large influx of calcium cause excitotoxicity?
calcium activates creation of polyamines, makes NO and radicals, makes proteases and endonucleases, and causes mito damage. ALL these things cause neuronal death
126
What besides damaging the neuron do polyamines do?
they modulate NMDA receptors to cause swelling of neuron due to increased permeability to sodium and thus neuronal death
127
Why kind of feedback do polyamines exhibit on NMDA receptors?
positive feedback
128
Excessive activation of NMDA glutamate receptors causes excitotoxicity and it is thought that this mechanism play a role in (blank) disorders such as (Blank)
neurodegenerative disorders
| Alzheimers disease
