Neurotransmitter Review Flashcards

1
Q

Steps in neurotransmitter release, action, and inactivation

A
  1. Calcium influx due to an action potential triggers
  2. Neurotransmitter release/ exocytosis
  3. Postsynaptic receptor (ion channel or GCPR)
  4. Presynaptic receptor
  5. Reuptake by a transporter (druggable target)
  6. Degredation (druggable target)
  7. Reuptake and metabolism by glia
  8. Vesicle membrane recycled (endocytosis so the membrane doesn’t get huge and floppy)
  9. Dense core granule vesicle (ie peptides)
  10. Release away from active zone
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2
Q

Where is acetylcholine found?

A

ACh is the neurotransmitter at all vertebrate neuromuscular junctions because all motor neurons are cholinergic. ACh is the neurotransmitter for all preganglionic neurons and parasympathetic postganglionic neurons because the autonomic nervous system is also cholinergic

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3
Q

Uses for acetylcholine

A

CNS circuits are also implicated in cognitive process such as attention, learning, memory, and arousal

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4
Q

The two main cholinergic pathways

A

the local circuit cells (those which are morphologically arrayed wholly within the neuronal structure in which they are found) and projection neurons (those that connect two or more regions).

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5
Q

ACh projections

A

Two important projections are in the basal forebrain cholinergic complex: medial septal nucleus (ms) and nucleus basilis (bas), both of which project to the hippocampus and cortex

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6
Q

What synthesizes ACh

A

ACh is synthesized by choline acetyltransferase

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7
Q

What degrades ACh

A

ACh is degraded by acetylcholinesterase

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8
Q

What is responsible for reuptake of ACh

A

The high affinity choline transporter (ChT) is responsible for reuptake of ACh

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9
Q

Details about the choline transporter

A

ChT has 13 transmembrane domains, with intracellular N and C terminals

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10
Q

Alzheimer’s disease

A

Alzheimer’s disease is a condition characterized by changes in cognition, attention, learning, and some types of memory. Muscarinic receptor antagonists disrupt short term memory. ChT and VAChT are lost (or there is at least a decreased ability to detect them). Three of the four FDA drugs approved for treatment of the symptoms of Alzheimer’s disease are cholinesterase inhibitors: galantamine, rivastigmine, and donepezil.

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11
Q

Cholinergic receptors

A

Cholinergic receptors include muscarinic (GPCR) and nicotinic (ligand gated ion channels)

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12
Q

Muscarinic receptors

A

Muscarinic receptors are densely concentrated in the brain; all subtypes are expressed (M1,3,5 is coupled with Gq and M2,4 is coupled with Gi).

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13
Q

Nicotinic receptors

A

Nicotinic receptors consist of five subunits oriented around a central cation channel

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14
Q

Nicotinic receptor types

A

Muscle type receptor: (α1)2β1ɣδ
Ganglion type receptor: (α3)2(β4)3
Neuronal receptor: (α4)2(β2)3 and (α7)5

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15
Q

Neuronal nicotinic receptor (α4)2(β2)3

A

This receptor is present pre and postsynaptically and has increased cation permeability to Na+ and K+. This neuronal subtype is responsible for high affinity binding of nicotine and has known pathological significance in addition to tobacco with Alzheimer’s disease. Activation is slow and desensitization is slow

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16
Q

Neuronal nicotinic receptor (α7)5

A

This receptor is present pre and postsynaptically and has increase cation permeability to Ca2+. It plays a role in schizophrenia and Alzheimer’s disease. Activation is fast and desensitization is fast

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17
Q

Role of catecholamines

A

arousal, mood, and central regulation of blood pressure

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18
Q

Examples of catecholamines in the brain

A

norepinephrine, dopamine, and epinephrine

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19
Q

Where does the locus ceruleus target

A

It targets the cerebral cortex, hippocampus, thalamic nuclei, cerebellum, and spinal cord

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20
Q

What is the purpose of locus ceruleus projections to the spinal cord?

A

Locus ceruleus projections to the spinal cord are thought to be important in regulation and processing of perceptual information

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21
Q

What are the lateral tegmental noradrenergic neurons

A

The lateral tegmental noradrenergic neurons are part of the reticular activating system and are important for arousal (why amphetamine causes arousal in humans). They are also important in the action of antidepressant drugs

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22
Q

What is the rate limiting step in the synthesis of norepinephrine?

A

tyrosine hydroxylase is the rate limiting step

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23
Q

What is responsible for the reuptake of norepinephrine?

A

norepinephrine transporter (NET)

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24
Q

What degrades norepinephrine in the presynaptic terminal?

A

MAO or COMT

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25
Q

Where is MAO located?

A

The outer mitochondrial membrane

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26
Q

What receptors is norepinephrine a substrate for?

A

α1, α2, β1, and β2 adrenoceptors

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27
Q

What is dopamine responsible for?

A

motor control, behavior control, and endocrine responses

28
Q

What are the categories of dopaminergic pathways?

A

The dopaminergic pathways are divided into three categories based on the length of efferent dopamine fibers: long, intermediate, and short

29
Q

What are the nuclei with long axon projections (DA)

A

Two important nuclei in the midbrain with long axon projections are the substantia nigra and the ventral tegmental area (VTA)

30
Q

DA pathway from substantia nigra

A

Dopamine containing neurons project from the substantia nigra to the striatum; this pathway degenerates in Parkinson’s disease. This led to the discovery of therapeutic effects of L-dopa in Parkinson’s disease and explains why the side effects of antipsychotic drugs mimic symptoms of Parkinson’s disease

31
Q

DA pathway from VTA

A

Neurons from the VTA project to the limbic structures and cerebral cortex. These are sometimes known as the mesolimbic and mesocortical pathways or forebrain bundle

32
Q

What are the DA pathways with intermediate axons?

A

The example of dopaminergic nuclei with intermediate axon projections is the arcuate nucleus of the hypothalamus to the intermediate lobe of the pituitary

33
Q

What are the DA pathways with short axons?

A

The examples of dopaminergic nuclei with short axon projections are the retina and olfactory bulb.

34
Q

What is the rate limiting enzyme in the synthesis of dopamine?

A

Tyrosine hydroxylase

35
Q

What facilitates the reuptake of dopamine

A

the dopamine transporter (DAT)

36
Q

What degrades dopamine?

A

MAO and COMT

37
Q

What are the primary metabolites of dopamine?

A

The primary metabolites of dopamine are homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC)

38
Q

Dopamine receptors and effects

A

Dopamine receptors are GPCR with seven transmembrane domains and multiple receptor subtypes. D1 and D5 are coupled to Gs and increase adenylate cyclase. D2,3,4¬ are coupled to Gi and decrease adenylate cyclase

39
Q

DAT

A

The dopamine transporter (DAT) is located on the presynaptic terminal and has 12 transmembrane domains. It is the target for cocaine, especially at the level of the nucleus accumbens.

40
Q

What is serotonin responsible for?

A

Serotonin is responsible for hallucinations, behavioral changes, sleep, wakefulness, mood, feeding behavior, control of sensory transmission (startle/avoidance/nociception), regulation of blood pressure, and sexual function

41
Q

What is the main serotonergic pathway?

A

The serotonergic pathways include nine nuclei, which collectively form the Raphe nuclei, and are clustered in the midline or raphe regions of the pons and upper brain stem and is where all serotonin is made. These serotonin containing cell bodies send ascending projections to the forebrain, especially limbic structures and cerebral cortex.

42
Q

What is the precursor for serotonin?

A

dietary tryptophan

43
Q

What is the rate limiting step in the synthesis of serotonin?

A

tryptophan hydroxylase

44
Q

What is the enzyme that converts L-dopa to dopamine?

A

Aromatic aminoacid decarboxylase

45
Q

What facilitates reuptake of serotonin?

A

serotonin reuptake transporter (SERT)

46
Q

What degrades serotonin?

A

MAO

47
Q

What is the metabolite of serotonin?

A

5-hydroxyindoleacetic acid (5-HIAA)

48
Q

Serotonin receptors

A

Serotonin receptors have multiple subtypes (5HT1 – 5HT7); all are GPCR except 5HT3, which is a ligand gated cation channel. In vivo 5HT3 agonists induce nausea and vomiting, this is thought to underlie the emetic side effects of cancer chemotherapy; therefore, the 5HT3 receptor is the target for antiemetic compounds

49
Q

What receptor does LSD target

A

5HT2

50
Q

SERT

A

The serotonin transporter is located on the presynaptic terminal and belongs to the family of biogenic amine transporters. It consists of 12 transmembrane domains and is the target of some classes of antidepressant drugs. Cocaine also has a high affinity for the serotonin transporter

51
Q

Glutamate

A

Glutamate is the main excitatory neurotransmitter in the brain and the hippocampus and the cortex have a lot of receptors

52
Q

GABA

A

The main inhibitory neurotransmitter in the brain

53
Q

Glycine

A

The main inhibitory neurotransmitter in the spinal cord

54
Q

What is the main source of glutamate?

A

The Krebs cycle

55
Q

What is the metabolism of glutamate?

A

It is decarboxylated to GABA or transaminated to glycine

56
Q

The glutamate transporter

A

The glutamate transporter has 12 transmembrane domains and specifically clears glutamate from the synapse (note that glutamate requires a tight synapse); many subtypes exist

57
Q

Types of glutamate receptors

A

There are two main families of glutamate receptors based on their signal transduction pathways: the ionotropic glutamate receptors (which are ligand gated ion channels) and the metabotropic receptors mGluR 1-8 (which are GPCRs).

58
Q

Ionotropic glutamate receptors

A

All of the members of the ionotropic glutamate receptor family has four subunits. They are classified based upon activation by synthetic glutamate analogues: NMDA or non-NMDA, which is further subdivided into AMPA-preferring or Kainate preferring. All three types of ionotropic glutamate receptors are composed of multiple subunits that assemble to form a central cation channel. Receptors allow the influx of cations, producing a rapid depolarization of the postsynaptic neuron

59
Q

What are the types of GABAergic neurons

A

There are two types of GABAergic neurons: short interneurons predominate and long GABAergic projection neurons

60
Q

How is GABA synthesized?

A

GABA is synthesized in a single step at the terminal by α-decarboxylation of L-glutamic acid by glutamic acid decarboxylase (GAD) expressed by GABAergic neurons

61
Q

What metabolizes GABA

A

GABA transaminase

62
Q

GABA receptors

A

GABAA and GABAC receptors are ligand gated ion channels. GABAB receptor is G-protein coupled and negatively coupled to adenylyl cyclase

63
Q

Baclofen

A

Baclofen is a GABAB receptor agonist, used to treat spasticity and muscle/motor disorders such as spasm, pain and stiffness associated with cerebral palsy or multiple sclerosis

64
Q

GABA A receptors

A

The GABAA receptor is a member of the superfamily of ligand gated ion channels. It is a heterooligomeric protein, composed of 5 subunits based on homology with nicotinic ACh receptor that span the cell membrane to form a chloride channel. Multiple subtypes of each subunit have been identified: α, β, ɣ, δ families

65
Q

How do benzodiazepines affect GABA receptors?

A

They increase the frequency of channel opening

66
Q

How do barbiturates affect GABA receptors?

A

Prolonged duration of channel opening

67
Q

GABA transporter

A

The GABA transporter has 12 transmembrane domains and is sodium dependent; it specifically clears GABA from the synapse. The glial transporter is distinct from that found in neurons