Neurotransmitter Systems Part 1 Flashcards
1
Q
These drugs induce 5HT release to procure sensory enhancement and empathy
A
Ecstasy (MDMA 3,4 methylene-dioxy-methamphetamine, MDEA 3,4 methylene-dioxy-ethamphetamine)
2
Q
This enzyme is also regulated at the RNA (transcriptional) level. Inc RNA synthesis of it occurs when a large amount of it is needed
A
tyrosine hydroxylase
3
Q
These types of receptors respond to ACh
A
Cholinergic receptors
4
Q
What is the rate limiting step in ACh synthesis?
A
Uptake of the choline
5
Q
What does the -ceptic prefix indicate?
A
That the cell has receptors for that NT
6
Q
This study uses agonists and antagonists to classify receptor subtypes (like ACh, glutamate, NE, GABA-A, GABA-B, etc)
A
Neuropharmacology
7
Q
This is activated by new, non-painful stimuli
A
NE
8
Q
These neurons modulate attention, feeding behavior, sleep, mood, arousal, learning, memory, and brain metabolism
A
Noradrenergic
9
Q
How is ACh removed from the synapse?
A
AChE breaks ACh into choline and acetic acid. The acetic acid floats off and the choline is put back into the cell through a choline transporter using Na to be used to make more ACh
10
Q
Cells that produce and release GABA are this
A
GABAergic
11
Q
This is taken up from the extracellular fluid by a specific transporter and put back into a neuron to make more ACh
A
Choline
12
Q
High affinity glutamate, dopamine, 5HT, NE, glycine, E, and GABA use these NT transporters
A
Membrane Na+
13
Q
These are used by applying them to a target neuron with a pipette and observing if the same response occurs as when the neuron is stimulated
A
Presumptive NT
14
Q
Amine (NE, E, 5HT, Dopa), ACh, IAAT (GABA and Glycine), and glutamate all used these NT transporters
A
Vesicular H+
15
Q
This NT acts through 1 transmitter gated and multiple GPCRs
A
5HT
16
Q
These neurons are widespread throughout the brain and work through GPCRs and ligand gated receptors. They can be found in areas like ganglion cells, sympathetic ganglion, and the adrenal gland
A
Cholinergic neurons
17
Q
This is a Na and Cl dependent transporter protein on synaptic membrane and on some vesicles that is the rate limiting step in ACh synthesis
A
Choline transporter
18
Q
What happens to receptors on neurons downstream from the neuron that switched its NT?
A
They change to match the new NT being released. They start making receptors for the new NT
19
Q
This transporter has a different structure than membrane or vesicular transporters
A
Choline transporter
20
Q
Each one of these can bind to different subtypes of receptors for it
A
NTs (ACh has over 20 transmitter gated receptors alone)
21
Q
This drug may inc function of 5-HT1A receptors
A
Prozac
22
Q
How can NT switching occur?
A
Can be due to experience/environment
23
Q
How does immunocytochemistry show if a neuron has a NT or not?
A
Neurons with the NT will show the antibody injected for that NT while neurons without it will not
24
Q
How can we test if a molecule produces a response in the postsynaptic cell (the postsynaptic cell has receptors) (3rd rule for identifying a NT)?
A
Presumptive NT applied to target neuron and electrophysiological response is recorded. This response is compared to the one that occurs when the presynaptic neuron is stimulated. If they match, it shows it is the presumptive NT
25
These are agonists of glutamatergic receptors at their specific types of receptors
AMPA, NMDA, Kainate
26
Most NTs fall into one of these 3 categories
1. Amino acids
2. Amines made from amino acids
3. Peptides
27
This is used as a NT in the brain and systemically by release from adrenal gland
Adrenaline (epinephrine)
28
Increased concentrations of this increases tyrosine hydroxylase activity which is consistent with increased synaptic activity
Ca2+
29
Treatments for some diseases like AD involve inc levels of this
Choline
30
These can be depolarized by K and the release of NT can be measured as a result. Ca can be present or not to test dependency for NT release
Slice culture or dissociated neurons
31
What does the amount of DA made depend on?
The amount of dopa available
32
These neurons are involved in mood, movement, attention, and autonomic functions
Catecholaminergic neurons
33
These type of neurons regulate pain signaling
Raphe nucleus neurons (serotonergic)
34
Where do serotonergic neurons originate from?
Raphe regions of pons and upper brainstem
35
This NT is removed from the synapse and destroyed like DA and NE
E
36
This is an agonist to the nicotinic ACh receptor
Nicotine
37
SLIDE 44!!!
SLIDE 44!!!
38
This is the most diffuse (widespread) throughout the brain out of all the NTs
NE
39
This method can be used to look at multiple RNA at once
In situ hybridization
40
Dopaminergic neurons coming from here are involved in motor function
Substantia nigra
41
What happens to a small portion of DA in the synapse (10%)?
It is degraded
42
Dopamine B-hydroxylase is present in these neurons inside synaptic vesicles instead of the cytosol like the other catecholamine enzymes
Adrenergic neurons
43
Cells that produce and release NE are this
Noradrenergic
44
Who coined the terms cholinergic and noradrenergic?
Dale
45
SLIDE 47
SLIDE 47
46
This type of neuron is present in few numbers but has widespread projections to the forebrain
Serotonergic neurons
47
Where do NE neurons in the locus coeruleus project to?
numerous structures including the cortex, hypothalamus, and hippocampus
48
These types of NTs all only use GPCRs
Catecholamines (DA, NE, E)
49
This type of analysis involves cloning many receptor cDNAs, DNA and RNA sequencing, and the discovery that the diversity and subtypes of receptors are larger than expected from binding and pharmacology
Molecular analysis
50
The activity of this is the rate limiting step in catecholamine synthesis
Tyrosine hydroxylase
51
Prozac inhibits reuptake of this NT
5HT
52
This NT is a precursor to melatonin in the pineal gland
5HT
53
The principle that each neuron only has one NT (often incorrect, violated by many neurons)
Dales principle
54
SLIDE 26
SLIDE 26
55
This is used to combine with choline to make ACh through choline acetyltransferase (ChAT)
Acetyl CoA
56
Long term use of ecstasy may lead to this
Destruction of serotonergic projections
57
Some non cholinergic neurons make this and some nerve gases and insecticides block this
Acetylcholinesterase (AChE)
58
Where is NE made and why?
It is made in vesicles bc that's where the dopamine B-hydroxylase enzyme is
59
This enzyme degrades ACh in the synaptic cleft and on axon membranes at a rate of 5000 degraded/second
Acetylcholinesterase (AChE)
60
These receptors use labeled ligands to bind specifically to receptors
Ligand binding (ligand gated)
61
These 3 catecholamine enzymes are made in the cytoplasm while this one is made in vesicles
```
Cytoplasm = tyrosine hydroxylase, dopa decarboxylase, and phentolamine N-methyltransferase
Vesicles = Dopamine B-hydroxylase
```
62
How does in situ hybridization show if a neuron has a NT or not?
Neurons with the NT will show the radioactive RNA that was used to locate the NT by being a complementary sequence of amino acid. The RNA is the thing that will be able to be detected, this method detects RNA
63
Dopaminergic neurons coming from here are involved in reward
Ventral tegmental area
64
The cellular response to 5HT depends on these
What type of GPCR is present, different GPCRs produce different responses
65
These 3 things can be classified as ligands and bind to ligand gated receptors
The NT, agonist, or antagonist
66
This NT is removed from the synaptic cleft by NET or DAT
NE
67
Cells that produce and release peptides are this
Peptidergic
68
What are the two major groups of cholinergic neurons in the brain?
Basal forebrain neurons and dorsolateral pontine tegmental constellation neurons
69
Short term use of ecstasy may lead to this
Tachycardia, hyperthermia, and dehydration
70
Where are the two places dopaminergic neurons start from?
Substantia nigra and Ventral tegmental area
71
These molecules can be toxins or components of venom that bind to ligand gated receptors
Ligands (snail, sanke, spider toxins/venom)
72
Method that detects RNA expression using a specific probe, labeled with radioactivity or colored or fluorescent product (used to show NTs are synthesized and stores in presynaptic neuron)
In situ hybridization
73
How is 5HT synthesized?
Tryptophan + tryptophan hydroxylase -->
5-hydroxytryptophan (5HTP) + 5HTP decarboxylase -->
5-hydroxytryptamine (5HT, serotonin)
74
Why is it difficult to stimulate a single neuron and determine what it is releasing in the CNS?
Many synapses using different NTs are close in proximity
75
This is an antagonist to the nicotinic ACh receptor
Curare
76
When can NT switching occur?
During development in CNS and neural crest and also in the mature CNS
77
Large amounts of this enzyme are seen in dopaminergic neurons bc it is needed to make DA
Dopa-decarboxylase
78
This NT acts through GPCRs
E
79
What is the filling of ACh vesicles driven by?
H+ gradient powered by H+-ATPase (2H+/ACh)
80
How is ACh pumped into vesicular ACh transporter vesicles and why is this allowed to happen?
ACh is pumped in by protons being pumped out. This can happen bc the inside of the vesicular ACh transporter vesicle is highly acidic
81
This NT can be recycled or broken down by MAO
NE
82
NT at neuromuscular junction, made by all motor neurons in spinal cord and brain
ACh
83
This NT is present in fewer neurons and it regulates cardiac and respiratory functions
E
84
These are synthesized in a consecutive pathway, needing one before making the next and the proper enzyme
Catecholamines
85
SLIDE 45
SLIDE 45
86
This NT works through 5 GPCRs
DA (D1-D5)
87
What is the order for catecholamine synthesis with their NTs?
```
Tyrosine + tyrosine hydroxlyase -->
Dopa + dopa decarboxylase -->
DA + dopamine B-hydroxylase -->
NE + phentolamine N-methyltransferase -->
E
```
88
Method that makes antibodies to specific NTs or enzymes which synthesize the NT (used to show NTs are synthesized and stored in presynaptic neuron)
Immunocytochemistry
89
What is a potential problem with immunocytochemistry and how is it solved?
Many NTs don't have an immune response which can be an issue, solved by making antibodies for enzymes instead of NTs
90
Examples of neurons violating Dales principle
Peptide containing neurons and dual transmitter neurons
91
This NT is transported back into the terminal, then reloaded or degraded by MAO
5HT
92
Do the transporters that take NTs out of synapses and the ones that load them into vesicles look similar?
No, they are structurally very different
93
These can be used to localize and quantify receptor subtypes
Ligands (NTs, agonists, antagonists, toxins, venom)
94
These types of neurons all act through GPCRs
Dopaminergic neurons
95
Dopamine, 5HT, NE, E, Glycine, and GABA use this specific membrane Na+ NT transporter
Na-Cl coupled
96
Where does brain tryptophan come from?
The blood
97
Fluid from these areas can be used to determine if a NT has been released from the presynaptic terminal in response to stimulation
Fluid from near axons or cells
98
These two NTs work through a family of GPCRs
NE and E
99
5HT uses this transporter to be loaded into vesicles, as do all other monoamines
Vesicular monoamine transporter
100
Can neurons switch the type of NT they express?
Yes
101
This NTs function in the CNS is not fully understood
E
102
This method can be used to activate specific population of neurons in the CNS to eliminate the problem of trying to stimulate a certain type of neuron to see what it releases
Optogenetics
103
What happens to the majority of DA in the synapse (90%)?
Reuptake
104
Where are major groups of adrenergic (E) cells found?
Medulla
105
These receptors respond to glutamate
Glutamatergic (AMPA, NMDA, Kainate)
106
This is the basis for Parkinson's disease treatment bc dopamine cant cross the BBB
Dopa, it can cross the BBB unlike dopamine
107
Where is E made and how?
It is made in the cytosol then put into vesicles bc NE must be released from its vesicle, then combine with PNMT to make E, which is then taken back up into vesicles
108
These neurons are widespread throughout the brain and originate from the raphe nuclei
Serotonergic neurons
109
Many circuits in the autonomic nervous system use these neurons
Cholinergic
110
Antibodies to enzymes in the synthesis pathway are used to identify these types of neurons
Catecholaminergic neurons
111
Unlike ACh, the majority of these NTs are transported back into the cell be specific Na dependent transporters
Catecholamines (DA, NE, E, 5HT)
112
What are basal forebrain cholinergic neurons involved in? Where are they found?
Learning, memory, and AD. Found in basal ganglia
113
These types of NT transporters are H+ dependent while these are Na+ dependent (and also sometimes H+ too)
H+ = Load into vesicles (SLC17, SLC18, SLC32 gene families)
| Na+ (sometimes H+) = Take out of synapse (SLC1 and SLC6 gene families)
114
What does the -ergic prefix indicate?
That the cell makes that NT
115
These drugs target 5HT reuptake and are used to treat depression
SSRIs (fluoxetine, prozac)
116
This NT doesn't have its own reuptake transporter so its uses others. It doesn't really do a whole lot
E
117
What are the two things that can happen to DA once it has been taken back up into the presynaptic neuron?
It can be reloaded into a vesicle or degraded my MAO in mitochondria
118
What are they two markers for cells with 5HT?
Tryptophan hydroxylase and 5HTP decarboxylase
119
What regulates tyrosine hydroxylase?
End-product inhibition. The products are used to inhibit the tyrosine hydorxylase from making more
120
This enzyme is required for synthesis of ACh and is a good marker for cholinergic neurons
Choline acetyltransferase (ChAT)
121
Two different types of these cant bind to the same receptor
NTs
122
We aren't sure how changes in filling of this are controlled but suspect it may be from changes in driving force or number of transporters per vesicle
Vesicular ACh transporter
123
This enzyme is a good marker for all catecholamine cells
Tyrosine hydroxylase (TH)
124
What degrades DA in the synapse?
Monoamine oxidases and COMT enzymes
125
Cells that produce and release ACh are this
Cholinergic
126
This NT is present at lower levels than other catecholamines
E (adrenergic neurons)
127
These neurons contain phentolamine N-methyltransferase, the enzyme required to make epinephrine (adrenaline)
Adrenergic neurons
128
The synthesis of this NT is regulated by the amount of tryptophan in the extracellular fluid
5HT
129
These two things are involved in a neuron switching NTs
Protein signals and electrical activity
130
All of these types of neurons contain tyrosine hydroxylase
Catecholaminergic neurons
131
These things block the action of reuptake of dopamine and can even cause it to run in reverse, releasing more dopamine
Amphetamines and cocaine
132
What was the first NT discovered and who discovered it?
ACh, Loewi
133
This is an antagonist to the muscarinic ACh receptor
Atropine
134
Cells that produce and release glutamate are this
Glutamatergic
135
What are dorsolateral pontine tegmental constellation cholinergic neurons involved in? Where are they found?
Excitability of sensory relay systems. Found in pons, brainstem area
136
How can fluorescently labeled antibodies show different neurons?
Different types of neurons will show up different colors
137
What are the 3 requirements for a molecule to be classified as a NT?
1. Must be synthesized and stored in presynaptic neuron
2. Must be released by presynaptic terminal in response to stimulation
3. When applied experimentally, molecule must produce a response in the postsynaptic cell as occurs in vivo, (postsynaptic cell has receptors)
138
The pharmacology of this is distinct from plasma membrane transporters
Vesicular ACh transporter
139
Major group of NE neurons are located here, which projects to numerous structures including the cortex, hypothalamus, and hippocampus
Locus coeruleus
140
How did Loewi identify ACh as the first NT?
He stimulated the vagus nerve connecting to the heart and then transferred the surrounding solution contents to another heart extracellular fluid and observed the second heart showing the same response. Took fluid from one and put it in another and observed same response, knew ACh was being released from vagus nerve as a result
141
This is an agonist to the muscarinic ACh receptor
Muscarine
