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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)

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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

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3
Q

These types of receptors respond to ACh

A

Cholinergic receptors

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4
Q

What is the rate limiting step in ACh synthesis?

A

Uptake of the choline

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5
Q

What does the -ceptic prefix indicate?

A

That the cell has receptors for that NT

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6
Q

This study uses agonists and antagonists to classify receptor subtypes (like ACh, glutamate, NE, GABA-A, GABA-B, etc)

A

Neuropharmacology

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7
Q

This is activated by new, non-painful stimuli

A

NE

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8
Q

These neurons modulate attention, feeding behavior, sleep, mood, arousal, learning, memory, and brain metabolism

A

Noradrenergic

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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

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10
Q

Cells that produce and release GABA are this

A

GABAergic

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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

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12
Q

High affinity glutamate, dopamine, 5HT, NE, glycine, E, and GABA use these NT transporters

A

Membrane Na+

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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

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14
Q

Amine (NE, E, 5HT, Dopa), ACh, IAAT (GABA and Glycine), and glutamate all used these NT transporters

A

Vesicular H+

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15
Q

This NT acts through 1 transmitter gated and multiple GPCRs

A

5HT

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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

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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

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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

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19
Q

This transporter has a different structure than membrane or vesicular transporters

A

Choline transporter

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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)

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21
Q

This drug may inc function of 5-HT1A receptors

A

Prozac

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22
Q

How can NT switching occur?

A

Can be due to experience/environment

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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

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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

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25
Q

These are agonists of glutamatergic receptors at their specific types of receptors

A

AMPA, NMDA, Kainate

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26
Q

Most NTs fall into one of these 3 categories

A
  1. Amino acids
  2. Amines made from amino acids
  3. Peptides
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27
Q

This is used as a NT in the brain and systemically by release from adrenal gland

A

Adrenaline (epinephrine)

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28
Q

Increased concentrations of this increases tyrosine hydroxylase activity which is consistent with increased synaptic activity

A

Ca2+

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29
Q

Treatments for some diseases like AD involve inc levels of this

A

Choline

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30
Q

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

A

Slice culture or dissociated neurons

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31
Q

What does the amount of DA made depend on?

A

The amount of dopa available

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32
Q

These neurons are involved in mood, movement, attention, and autonomic functions

A

Catecholaminergic neurons

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33
Q

These type of neurons regulate pain signaling

A

Raphe nucleus neurons (serotonergic)

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34
Q

Where do serotonergic neurons originate from?

A

Raphe regions of pons and upper brainstem

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35
Q

This NT is removed from the synapse and destroyed like DA and NE

A

E

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36
Q

This is an agonist to the nicotinic ACh receptor

A

Nicotine

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37
Q

SLIDE 44!!!

A

SLIDE 44!!!

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38
Q

This is the most diffuse (widespread) throughout the brain out of all the NTs

A

NE

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39
Q

This method can be used to look at multiple RNA at once

A

In situ hybridization

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40
Q

Dopaminergic neurons coming from here are involved in motor function

A

Substantia nigra

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41
Q

What happens to a small portion of DA in the synapse (10%)?

A

It is degraded

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42
Q

Dopamine B-hydroxylase is present in these neurons inside synaptic vesicles instead of the cytosol like the other catecholamine enzymes

A

Adrenergic neurons

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43
Q

Cells that produce and release NE are this

A

Noradrenergic

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44
Q

Who coined the terms cholinergic and noradrenergic?

A

Dale

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45
Q

SLIDE 47

A

SLIDE 47

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46
Q

This type of neuron is present in few numbers but has widespread projections to the forebrain

A

Serotonergic neurons

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47
Q

Where do NE neurons in the locus coeruleus project to?

A

numerous structures including the cortex, hypothalamus, and hippocampus

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48
Q

These types of NTs all only use GPCRs

A

Catecholamines (DA, NE, E)

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49
Q

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

A

Molecular analysis

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50
Q

The activity of this is the rate limiting step in catecholamine synthesis

A

Tyrosine hydroxylase

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51
Q

Prozac inhibits reuptake of this NT

A

5HT

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52
Q

This NT is a precursor to melatonin in the pineal gland

A

5HT

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53
Q

The principle that each neuron only has one NT (often incorrect, violated by many neurons)

A

Dales principle

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54
Q

SLIDE 26

A

SLIDE 26

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55
Q

This is used to combine with choline to make ACh through choline acetyltransferase (ChAT)

A

Acetyl CoA

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56
Q

Long term use of ecstasy may lead to this

A

Destruction of serotonergic projections

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57
Q

Some non cholinergic neurons make this and some nerve gases and insecticides block this

A

Acetylcholinesterase (AChE)

58
Q

Where is NE made and why?

A

It is made in vesicles bc that’s where the dopamine B-hydroxylase enzyme is

59
Q

This enzyme degrades ACh in the synaptic cleft and on axon membranes at a rate of 5000 degraded/second

A

Acetylcholinesterase (AChE)

60
Q

These receptors use labeled ligands to bind specifically to receptors

A

Ligand binding (ligand gated)

61
Q

These 3 catecholamine enzymes are made in the cytoplasm while this one is made in vesicles

A 
Cytoplasm = tyrosine hydroxylase, dopa decarboxylase, and phentolamine N-methyltransferase
Vesicles = Dopamine B-hydroxylase
62
Q

How does in situ hybridization show if a neuron has a NT or not?

A

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
Q

Dopaminergic neurons coming from here are involved in reward

A

Ventral tegmental area

64
Q

The cellular response to 5HT depends on these

A

What type of GPCR is present, different GPCRs produce different responses

65
Q

These 3 things can be classified as ligands and bind to ligand gated receptors

A

The NT, agonist, or antagonist

66
Q

This NT is removed from the synaptic cleft by NET or DAT

67
Q

Cells that produce and release peptides are this

A

Peptidergic

68
Q

What are the two major groups of cholinergic neurons in the brain?

A

Basal forebrain neurons and dorsolateral pontine tegmental constellation neurons

69
Q

Short term use of ecstasy may lead to this

A

Tachycardia, hyperthermia, and dehydration

70
Q

Where are the two places dopaminergic neurons start from?

A

Substantia nigra and Ventral tegmental area

71
Q

These molecules can be toxins or components of venom that bind to ligand gated receptors

A

Ligands (snail, sanke, spider toxins/venom)

72
Q

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)

A

In situ hybridization

73
Q

How is 5HT synthesized?

A

Tryptophan + tryptophan hydroxylase –>
5-hydroxytryptophan (5HTP) + 5HTP decarboxylase –>
5-hydroxytryptamine (5HT, serotonin)

74
Q

Why is it difficult to stimulate a single neuron and determine what it is releasing in the CNS?

A

Many synapses using different NTs are close in proximity

75
Q

This is an antagonist to the nicotinic ACh receptor

76
Q

When can NT switching occur?

A

During development in CNS and neural crest and also in the mature CNS

77
Q

Large amounts of this enzyme are seen in dopaminergic neurons bc it is needed to make DA

A

Dopa-decarboxylase

78
Q

This NT acts through GPCRs

79
Q

What is the filling of ACh vesicles driven by?

A

H+ gradient powered by H+-ATPase (2H+/ACh)

80
Q

How is ACh pumped into vesicular ACh transporter vesicles and why is this allowed to happen?

A

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
Q

This NT can be recycled or broken down by MAO

82
Q

NT at neuromuscular junction, made by all motor neurons in spinal cord and brain

83
Q

This NT is present in fewer neurons and it regulates cardiac and respiratory functions

84
Q

These are synthesized in a consecutive pathway, needing one before making the next and the proper enzyme

A

Catecholamines

85
Q

SLIDE 45

86
Q

This NT works through 5 GPCRs

A

DA (D1-D5)

87
Q

What is the order for catecholamine synthesis with their NTs?

A 
Tyrosine + tyrosine hydroxlyase -->
Dopa + dopa decarboxylase -->
DA + dopamine B-hydroxylase -->
NE + phentolamine N-methyltransferase -->
E
88
Q

Method that makes antibodies to specific NTs or enzymes which synthesize the NT (used to show NTs are synthesized and stored in presynaptic neuron)

A

Immunocytochemistry

89
Q

What is a potential problem with immunocytochemistry and how is it solved?

A

Many NTs don’t have an immune response which can be an issue, solved by making antibodies for enzymes instead of NTs

90
Q

Examples of neurons violating Dales principle

A

Peptide containing neurons and dual transmitter neurons

91
Q

This NT is transported back into the terminal, then reloaded or degraded by MAO

92
Q

Do the transporters that take NTs out of synapses and the ones that load them into vesicles look similar?

A

No, they are structurally very different

93
Q

These can be used to localize and quantify receptor subtypes

A

Ligands (NTs, agonists, antagonists, toxins, venom)

94
Q

These types of neurons all act through GPCRs

A

Dopaminergic neurons

95
Q

Dopamine, 5HT, NE, E, Glycine, and GABA use this specific membrane Na+ NT transporter

A

Na-Cl coupled

96
Q

Where does brain tryptophan come from?

97
Q

Fluid from these areas can be used to determine if a NT has been released from the presynaptic terminal in response to stimulation

A

Fluid from near axons or cells

98
Q

These two NTs work through a family of GPCRs

99
Q

5HT uses this transporter to be loaded into vesicles, as do all other monoamines

A

Vesicular monoamine transporter

100
Q

Can neurons switch the type of NT they express?

101
Q

This NTs function in the CNS is not fully understood

102
Q

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

A

Optogenetics

103
Q

What happens to the majority of DA in the synapse (90%)?

104
Q

Where are major groups of adrenergic (E) cells found?

105
Q

These receptors respond to glutamate

A

Glutamatergic (AMPA, NMDA, Kainate)

106
Q

This is the basis for Parkinson’s disease treatment bc dopamine cant cross the BBB

A

Dopa, it can cross the BBB unlike dopamine

107
Q

Where is E made and how?

A

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
Q

These neurons are widespread throughout the brain and originate from the raphe nuclei

A

Serotonergic neurons

109
Q

Many circuits in the autonomic nervous system use these neurons

A

Cholinergic

110
Q

Antibodies to enzymes in the synthesis pathway are used to identify these types of neurons

A

Catecholaminergic neurons

111
Q

Unlike ACh, the majority of these NTs are transported back into the cell be specific Na dependent transporters

A

Catecholamines (DA, NE, E, 5HT)

112
Q

What are basal forebrain cholinergic neurons involved in? Where are they found?

A

Learning, memory, and AD. Found in basal ganglia

113
Q

These types of NT transporters are H+ dependent while these are Na+ dependent (and also sometimes H+ too)

A

H+ = Load into vesicles (SLC17, SLC18, SLC32 gene families)

Na+ (sometimes H+) = Take out of synapse (SLC1 and SLC6 gene families)

114
Q

What does the -ergic prefix indicate?

A

That the cell makes that NT

115
Q

These drugs target 5HT reuptake and are used to treat depression

A

SSRIs (fluoxetine, prozac)

116
Q

This NT doesn’t have its own reuptake transporter so its uses others. It doesn’t really do a whole lot

117
Q

What are the two things that can happen to DA once it has been taken back up into the presynaptic neuron?

A

It can be reloaded into a vesicle or degraded my MAO in mitochondria

118
Q

What are they two markers for cells with 5HT?

A

Tryptophan hydroxylase and 5HTP decarboxylase

119
Q

What regulates tyrosine hydroxylase?

A

End-product inhibition. The products are used to inhibit the tyrosine hydorxylase from making more

120
Q

This enzyme is required for synthesis of ACh and is a good marker for cholinergic neurons

A

Choline acetyltransferase (ChAT)

121
Q

Two different types of these cant bind to the same receptor

122
Q

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

A

Vesicular ACh transporter

123
Q

This enzyme is a good marker for all catecholamine cells

A

Tyrosine hydroxylase (TH)

124
Q

What degrades DA in the synapse?

A

Monoamine oxidases and COMT enzymes

125
Q

Cells that produce and release ACh are this

A

Cholinergic

126
Q

This NT is present at lower levels than other catecholamines

A

E (adrenergic neurons)

127
Q

These neurons contain phentolamine N-methyltransferase, the enzyme required to make epinephrine (adrenaline)

A

Adrenergic neurons

128
Q

The synthesis of this NT is regulated by the amount of tryptophan in the extracellular fluid

129
Q

These two things are involved in a neuron switching NTs

A

Protein signals and electrical activity

130
Q

All of these types of neurons contain tyrosine hydroxylase

A

Catecholaminergic neurons

131
Q

These things block the action of reuptake of dopamine and can even cause it to run in reverse, releasing more dopamine

A

Amphetamines and cocaine

132
Q

What was the first NT discovered and who discovered it?

A

ACh, Loewi

133
Q

This is an antagonist to the muscarinic ACh receptor

134
Q

Cells that produce and release glutamate are this

A

Glutamatergic

135
Q

What are dorsolateral pontine tegmental constellation cholinergic neurons involved in? Where are they found?

A

Excitability of sensory relay systems. Found in pons, brainstem area

136
Q

How can fluorescently labeled antibodies show different neurons?

A

Different types of neurons will show up different colors

137
Q

What are the 3 requirements for a molecule to be classified as a NT?

A
  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
Q

The pharmacology of this is distinct from plasma membrane transporters

A

Vesicular ACh transporter

139
Q

Major group of NE neurons are located here, which projects to numerous structures including the cortex, hypothalamus, and hippocampus

A

Locus coeruleus

140
Q

How did Loewi identify ACh as the first NT?

A

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
Q

This is an agonist to the muscarinic ACh receptor

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