Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neuro Week 2 > ICL 2.9: CNS Neurotransmitter Systems > Flashcards

ICL 2.9: CNS Neurotransmitter Systems Flashcards

1
Q

what is the function of astrocytes with neurotransmitters?

A

they regulate neurotransmitters

so if there’s excess glutamate they’ll pick it up and get rid of it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is the dominant mode of synaptic transmission in the CNS?

A

chemical synapses

aka neurotransmitters!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what does a chemical synapse look like?

A

presynaptic side: axon terminal contains synaptic vesicles, located adjacent to the terminal’s active zone

postsynaptic side: postsynaptic density (postsynaptic membrane specialization)

pre- and postsynaptic side are separated by the synaptic cleft (width = 20-50 nm)

signals travel from “pre” to “post” synaptic neuron

the signal is chemical in nature and consists of a neurotransmitter that crosses the synaptic cleft (intercellular signal), and is converted into an intracellular signal on the postsynaptic side

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is a neuromuscular junction?

A

motor neuron-muscle junction

if there’s degeneration of the motor neuron or the myelin sheath of the axon, the muscle will be weak or have slower transmission

ex. ALS = motor neuron degeneration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are the 3 types of neurotransmitters?

A
  1. amines
  2. amino acids
  3. peptides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

where are peptide neurotransmitters synthesized?

A

rough ER

then they go to the golgi apparatus to be modified

now you have active peptide NTs and they’ll be put in secretory granules and stored in the synaptic vesicles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what would cause NT release from the presynaptic neuron?

A
  1. “at rest”, the synapse (presynaptic side) contains numerous synaptic vesicles filled with neurotransmitter, intracellular calcium levels are very low
  2. arrival of an action potential: voltage-gated calcium channels open, calcium enters the synapse
  3. calcium triggers exocytosis and release of neurotransmitter
  4. vesicles are recycled by endocytosis

so if there’s a Ca+2 shortage, NTs won’t be released!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are the two main classes of receptors found on post-synaptic neurons?

A
  1. ionotropic

2. metabotropic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what are ionotropic receptors?

A

transmitter-gated ion channels

transmitter molecules bind on the outside and cause the channel to open and become permeable to either Na+ (depolarizing, excitatory effect) or Cl– (hyperpolarizing, inhibitory effect)

the receptor itself is the channel

ex. GABA-A neurotransmitter will have an inhibitory effect by causing a Cl- influx

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are metabotropic receptors?

A

G-protein-coupled receptors = secondary messengers

these receptors have slower, longer-lasting and diverse postsynaptic effects

these receptors can have effects that change an entire cell’s metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what are the two possible effects on a neuron that an ionotropic receptor can have?

A
  1. EPSP = Excitatory Post-Synaptic Potential

this will happen if there’s a Na+ influx which will depolarize the neuron

  1. IPSP = Inhibitory Post-Synaptic Potential

this will happen if there’s a Cl- influx which will hyper polarize the neuron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what two possible effects does a metabotropic receptor have on a postsynaptic neuron?

A
  1. neurotransmitter binds to receptor, which activates G-proteins, which in turn activates some other “effector” ion channel
  2. neurotransmitter binds to receptor and then the G-protein activates an “effector” enzyme which produces a secondary messenger that goes and does something

so you can either have direct activation of an ion channel by a G protein or some long-winded secondary messenger cascade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what is the shortcut pathway?

A

direct activation of a local ion channel by a G protein via a metabotropic receptor

ex. activation of G-protein in the heart by the binding of Ach to the metabotropic receptor –> then the G protein goes and activates a nearby potassium channel to open

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are the 3 ways that NTs are removed from the synaptic cleft?

A
  1. diffusion away from the synapse
  2. reuptake = neurotransmitter re-enters presynaptic axon terminal
  3. enzymatic destruction inside terminal cytosol or synaptic cleft
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

which neurotransmitters are amino acids?

A
  1. Glutamate (glutamatergic) = excitatory
  2. GABA (GABAergic) = inhibitory
  3. Glycine = modulatory (always with glutamate)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

which neurotransmitters are amines?

A
  1. acetylcholine (cholinergic) (only neurotransmitter not made from amino acids)
  2. norepinephrine (noradrenergic)
  3. dopamine (dopaminergic)
  4. serotonin (serotonergic)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

which neurotransmitters are peptides?

A
  1. substance P
  2. dynorphin
  3. enkephalins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

which receptor do neurotransmitters bind to?

A

neurotransmitter binds to specific receptors

no two neurotransmitters bind to the same receptors

but one neurotransmitter can bind to many different receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is the cholinergic system?

A

acetylcholine (Ach) is the neurotransmitter at the neuromuscular junction synthesized by all the motor neurons in the spinal cord and brainstem

acetylcholine contributes also to specific circuits in the PNS and CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what breaks down acetylcholine? what makes acetylcholine?

A

acetylcholinesterase

it breaks ACh into choline and acetic acid

JUST choline is then transported back into the presynaptic neuron and turned back into ACh by choline acetyltransferase
so it can be released again

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what are the two acetylcholine receptors?

A
  1. muscarinic

mediates slow response

  1. nicotinic

mediates fast response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what substance blocks muscarinic receptors?

A

atropine is an ACh antagonist

muscarinic receptors bind ACh

atropine is used to keep the heart pumping

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what substance blocks nicotinic receptors?

A

curare is an ACh antagonist

nicotinic receptors bind ACh receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what is Huntington’s disease?

A

dysfunction of cholinergic system as a consequence of degeneration of GABAergic neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what is used to treat Alzheimer’s disease?

A

acetylcholinesterase inhibitors

ex. Donepezil, galantamine, rivastigmine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what is the MOA of the drugs used to treat Parkinson’s?

A

anticholinergic drugs decrease the excitatory actions of cholinergic neurons in the striatum

ex. Benztropine (Cogentin®) and trihexyphenidyl

27
Q

which disease involve the acetylcholine receptors?

A
  1. Huntington’s .
  2. Alzheimer’s
  3. Parkinson’s
28
Q

what is the glutamatergic system?

A

glutamate is the major excitatory amino acids in the CNS

glutamate has a prominent role in synaptic plasticity, learning, and memory

excessive synaptic glutamate is neurotoxic though because the neuron will be overstimulated

glial cells or astrocytes regulate extracellular glutamate through glutamate transporter 1 (GLT-1) and cystine/glutamate antiporter –> these two receptors on astrocytes modulate extra glutamate and break it down into glutamine then transport it back into the neuron

29
Q

how is glutamate synthesized?

A

enzymes = Krebs cycle enzymes and various transaminases: glutaminase

precursors = glucose, glutamine

30
Q

how is glutamate broken down/recycled?

A
  1. reuptake of glutamate

2. GAD (glutamic acid decarboxylase) – gives rise to GABA but only in GABA neurons

31
Q

what are the glutamate receptors?

A

IONOTROPIC
1. NMDA** (N-methyl-D-aspartate)

  1. AMPA** (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, previously called quisquakate)
  2. Kainate

METABOTROPIC
1. mGluR1 and mGluR5 – coupled to IP3

  1. mGluR2 and mGluR3 – negatively coupled to adenylyl cyclase
  2. mGluR4, mGluR6, mGluR7 and mGluR8 – inhibit cyclase
32
Q

how does the NMDA receptor work?

A

NMDA is an ionotropic receptor

at the resting potential (postsynaptic neuron), glutamate binds to the NMDA channel, the channel opens, but it is “plugged” by a magnesium ion (Mg2+)

depolarization of the postsynaptic membrane relieves the Mg2+ blockade and the channel opens to allow passage of sodium, potassium and calcium

this excites the postsynaptic neuron!

33
Q

what drug is a NMDA receptor antagonist?

A

phencyclidine = PCP!

34
Q

which diseases are related to glutamate receptors?

A
  1. schizophrenia
  2. neurodegenerative diseases –> excess glutamate lead to neurotoxicity
  3. convulsive disorders
  4. memory problems –> glutamate plays a key role in learning and memory
  5. cerebral ischemia and stroke –> due to excess of glutamate
  6. drugs
35
Q

how is schizophrenia related to glutamate receptors?

A

NMDA receptor antagonist, phencyclidine (PCP), causes symptoms similar to those of schizophrenia but note that the drug also activates D2 receptors

you use D2 antagonist to treat schizophrenia

36
Q

how is GABA synthesized?

A

enzymes = glutamic acid decarboxylase (GAD)

precursors = glucose, glutamic acid, glutamine

37
Q

what are the GABA receptors?

A

GABA(A)

GABA(B)

38
Q

how is GABA inactivated/recycled?

A
  1. reuptake of GABA by the neuronal and glia

2. GABA-transaminase break it down to glutamate and succinate

39
Q

what binds to GABA(A) receptors?

A
  1. ethanol
  2. benzodiazepines (BDZ)
  3. barbiturates (can stimulate the receptor without GABA!)

once these bind, they facilitate the action of GABA which will allow Cl- to enter the cell and inhibit action potentials by hyper polarizing the cell

so if you give someone benzodiazepine or they’re drinking alcohol, you have to be careful because they could end up in a coma or dead

40
Q

what is the structure of the GABA(B) receptor?

A

GABAB receptor is a G-protein-coupled receptor central to inhibitory neurotransmission in the brain

it functions as an obligatory heterodimer of the subunits GBR1 and GBR2

when GABA(B) is activated, it will trigger K+ to leave the cell and Ca+2 to enter the cell

41
Q

what diseases are related to GABA?

A
  1. Huntington’s –>degeneration of GABAergic neurons in striatum and connected brain regions
  2. convulsive disorders –> Benzodiazepine such as Lorazpem binds to GABA-A receptor for acute seizure treatment and Tiagabine (Gabitril ®), GABA transporter 1(GAT-1) for treatment of focal seizures
  3. dystonia –> Baclofen, GABA-B receptor agonist; and Benzodiazepines, GABA-A receptor agonists
  4. anxiety disorders –> Benzodiazepines, GABA-A receptor agonists
  5. neuropathic pain –> Baclofen, GABA-B receptor agonist
42
Q

what is the function of serotonin?

A

an amine neurotransmitter that regulates mood, emotional behavior, sleep, appetite

43
Q

how is serotonin synthesized?

A

tryptophan hydroxylase converts tryptophan into 5-HTP

then 5-HTP decarboxylase converts 5-HTP to 5-HT (serotonin)

this is good because tryptophan is regular found in food!

44
Q

how is serotonin broken down/inactivated?

A
  1. reuptake of 5-HT –> so lots of meds bind to and block the receptors that are re-uptaking serotonin to treat depression, sleep problems, etc.
  2. monoamine oxidase (MAO) – gives rise to 5-hydroxyindoleacetic acid (5-HIAA) (this is the major route)
  3. N-acetyltransferase – gives rise to N-acetylserotonin, then hydroxyindole-o-methyltransferase to give melatonin
45
Q

what does MAO-A do?

A

it metabolizes tyramine, norepinephrine, serotonin and dopamine

MAO-B mainly metabolizes DA

46
Q

what are the serotonin receptors?

A

5-HT1 family (1A, 1B, 1C) – all G-protein linked to inhibition of adenylate cyclase. Function as both autoreceptors and postsynaptic (heteroreceptors) receptors

5-HT2 family (2A, 2B and 2C) – stimulate phosphoinisitol (PI) turnover

5-HT3 family – (3A, 3B and 3C) intrinsic cation channel – emesis

5-HT4 and 5-HT7 – G-protein linked to stimulation of adenylate cyclase

5-HT1E and 5-HT1F coupled to Gi-proteins

5-HT5 family (A and B) coupled to Gi-proteins

5-HT6 coupled to Gs-proteins

47
Q

what are the important main serotonin receptors?

A

5-HT1A and 5-HT1B receptors expressed in presynaptic serotonergic neurons are called “autoreceptors”

5-HT receptors expressed in postsynaptic are called “heteroreceptors”

48
Q

what are the clinical applications of serotonin?

A
  1. depression: Deficit in 5-HT is among the cause of depressive state; so Selective Serotonin reuptake inhibitors (SSRIs), MAOIs, and Tricyclic antidepressants (TCA) can be used to treat depression
  2. anxiety disorder: 5-HT1A partial agonists (e.g. Buspirone) and SSRIs
  3. alcoholism: may involve deficiency in 5-HT
  4. eating disorders: deficiency in 5-HT
  5. sleeping disorders: 5-HT has a critical role in the sleep stages and cycles during the sleep time
  6. migraine: deficit in 5-HT is linked to migraine; treatment with 5-HT1B agonists (Triptans, e.g. Sumatriptan)
  7. suicide: deficiency in 5-HT
  8. schizophrenia: Atypical antipsychotics blocking 5-HT2 are used for the treatment of positive and negative symptoms of schizophrenia

examples of drugs: 5-HT2A antagonist and D2 antagonist such as Risperidone (Risperdal®), and 5-HT2A antagonist and partial D2 agonist such as Aripiprazole (Abilify®)

49
Q

what are selective serotonin reuptake inhibitors?

A

they prevent the reuptake of serotonin

SSRIs have fewer side-effects which allow newer drugs to be marketed for diverse disorders related to depression, such as the anxiety disorders, panic disorder, and obsessive-compulsive disorder (OCD)

however, serious drug interactions with MAO inhibitors and with tricyclic antidepressants can lead to Serotonin Syndrome – this includes cognitive-behavioral and autonomic symptoms like:

  1. confusion, agitation, hypomania
  2. sweating, hypertension, hyperthermia, nausea, diarrhea
  3. tremor, rigidity, hyperreflexia, restlessness, myoclonus
50
Q

how do you treat serotonin syndrome?

A

serious drug interactions with MAO inhibitors and with tricyclic antidepressants can lead to Serotonin Syndrome – this includes cognitive-behavioral and autonomic symptoms

treatment of serotonin syndrome may include:

  1. benzodiazepine, such as diazepam (Valium) or lorazepam (Ativan) to decrease agitation and muscle stiffness.
  2. cyproheptadine (Periactin), a drug that blocks serotonin production.
  3. withdrawal of medications that caused the syndrome.
51
Q

which amine neurotransmitters is tyrosine a precursor of?

A
  1. dopamine
  2. norepinephrine
  3. epinephrine

all of this are catecholamines and are involved in movement, mood, attention, and visceral function

52
Q

what is the function of tyrosine hydroxylase?

A

TH catalyzes the first step in catecholamine synthesis (dopamine, norepinephrine, epinephrine)

the activity of tH is the rate limiting step for catecholamine synthesis

tH is regulated by carious signals in the cytosol of the axon terminal

53
Q

how is dopamine synthesized?

A

enzymes = tyrosine hydroxylase; L-3,4-dihydroxyphenylalanine (DOPA) decarboxylase

precursors = phenylalanine, tyrosine, DOPA

L-DOPA therapy is used in the treatment of Parkinson’s disease

54
Q

what are the dopamine receptors?

A

D1

D2

55
Q

how is dopamine broken down/inactivated?

A
  1. Reuptake of DA

2. MAO – gives rise to 3,4-Dihydroxyphenylacetic acid (DOPAC)

56
Q

what are the clinical applications of dopamine?

A
  1. schizophrenia: Dopamine 2 (D2) receptors blockers for treatment of schizophrenic symptoms.
  2. Huntington’s disease: Dopamine blockers to control chorea.
  3. Parkinson’s disease: L-DOPA, dopamine agonists, MAO-inhibitors, drugs increasing dopamine metabolism.
  4. depression: dopamine reuptake blockers [Bupropion (Wellbutrin®, Zyban®)].
  5. smoking cessation: dopamine reuptake blockers [Bupropion (Wellbutrin®, Zyban®)].
57
Q

how do you treat ADHD?

A
  1. competitive reuptake inhibition with dopamine (substrate for DA transporter)
  2. facilitates the movement of DA out of vesicles
  3. promotes DAT-mediated reverse-transport of DA into the synaptic cleft independently of action-potential-induced vesicular release
    ex. adderall
58
Q

what are the norepinephrine receptors?

A
  1. Alpha (1 and 2)

2. Beta (1 and 2)

59
Q

how is norepinephrine broken down/inactivated?

A
  1. uptake of norepinephrine (NE)

2. MAO – to give rise to a glycol or acid

60
Q

what are the clinical applications of norepinephrine?

A
  1. depression: Tricyclic and atypical antidepressants, inhibitors of reuptake of NE as well as 5-HT.
  2. sleep Disorders: NE is modulating the sleep cycle with 5-HT and acetylcholine.
  3. eating disorders: deficiency in NE.
61
Q

what things are neuropeptides and what is their function?

A
  1. Neuropeptide Y
  2. Substance P
  3. Dynorphin
  4. Enkephalins

function in the nervous system = Neurotransmitter, Neuromodulator, Neurohormone

62
Q

what transporters reuptake neurotransmitters back into the presynaptic neuron?

A
  1. Vesicular transporter (A)
  2. Neuronal membrane transporter (B)

many psychoactive drugs block transporters and create imbalances that affect mood and behavior (e.g. cocaine blocking NE and DA uptake), but also antidepressants (e.g. fluoxetine (Prozac), an SSRI, blocking serotonin re-uptake)

63
Q

what are endocanabinoids?

A

encocannabinoids are endogenous cannabinoids, released from postsynaptic neurons and act on presynaptic terminals

communication from “post” to “pre” is called retrograde signaling.

endocannabinoids are retrograde messengers

retrograde messengers: feedback system to modulate the ordinary synaptic transmission

so endocanabinoids go and stimulatte CB1 receptors on the presynaptic neuron which inhibits the release of glutamate and GABA = it’s a neuromodulator!

the active ingredient of cannabis is ∆9-tetrahydrocannabinol (∆9-THC) binds to cannabinoid CB1 receptors on pre-synaptic nerve terminals in the brain

∆9-THC binding to CB1 receptors activates G-proteins that activate/inhibit a number of signal transduction pathway

Neuro Week 2 (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions