Brainscape's Knowledge GenomeTM

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


See full index

Molecular + Cellular Neuro > Synaptic Transmission + Cellular Signalling > Flashcards

Synaptic Transmission + Cellular Signalling Flashcards

1
Q

Acetylcholine locations/function in CNS + PNS (3)

A
  • Neurotransmitter in CNS and PNS

PNS:
* Cardiac function
* NMJ

CNS:
* Cognition
* Movement
* Conserved across various species
(evolutionary)

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

Allergic toxicity and Ach (2)

A
  • allergic toxicity can result from various diff things (eg insecticides, nerve agents, medications, mushrooms etc.)
  • common form of cholinergic toxicity is exposure to organic phosphates or carbonation insecticides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

nature -> drug egs (2)

A

belladonna: get atripine from it (overdoses = PNS symptoms - tremors, tachycardia etc)

tubocurarine: non-depolarising neuromuscular blocking agent - reduces amount of anaesthesia needed in surgery to elicit same effects

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

Ach in synapse steps (6)

A

1) packaged into vescicles (VAChT)
2) fuses w/membrane + released into synaptic cleft
3) ACh –> Choline + acetyl (by ACh esterase)
4) re-uptake via Acetyl transferase
5) converted back into ACh
6) packaged into vescicles (VAChT)

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

What is the rate limiting step in ACh synthesis? (1)

A

the uptake of choline from synaptic cleft into pre-synaptic membrane via NACh r

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Main cholinergic pathways (3)

A
  • Basal forebrain complex innervates
  • Hippocampus
  • Frontal cortex
  • Olfactory bulb
  • Medial habenula
  • Pedunculopontine
  • VTA
  • Thalamus
  • Cerebellum
  • Laterodorsal tegmental areas
  • Medial habenula
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Cholinergic receptors classification (5)

A

1)Nicotinic:
—> Neuronal (Nn) -> Adrenal, Immune cells, CNS, Ganglia
—-> Non-neuronal/skeletal (Nm)

2)Muscarinic:
—> M1, M3, M5
—>M2, M4

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

Nicotine info (6)

A
  • The psychoactive ingredient of tobacco
  • Naturally produced alkaloid
  • Present in the seeds of theNicotiana tabacum plant
  • It binds to nAChRs in the brain
  • Acts as an stimulant and anxiolytic
  • It is highly addictive
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Nicotinic acetylcholine receptors (nAChRs) info (5)

A
  • found through the CNS and play an important role in many functions
  • nAChRs are ligand-gated cation channels permeable to Na+, K+ and Ca 2+ ions
  • Pentamers formed as homomeric or heteromeric combinations of α (α2–7)and β (β2–4) subunits
  • Subunit combinations affect things such as drug affinity
  • After activation by an agonist, nAChRs enter a desensitized state, which limits the duration of nicotine’s acute effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

nAChRs locations (6)

A

nAChRs are distributed widely throughout the brain

  • Are located pre- and postsynaptically
  • Presynaptic nAChRs usually facilitate the release of other
    neurotransmitters(glutamate, dopamine and GABA)
  • Postsynaptic nAChRs (on NMJ in Somatic NS) mediate fast excitatory transmission
  • also located in the ganglia of the autonomic nervous system (sympathetic and parasympathetic).

locations:
* Cerebral cortex
* Hippocampus (memory + learning)
* Basal ganglia (addiction)
* Substantia nigra (addiction)
* Ventral tegmental area (VTA) (addiction)
* Nucleus accumbens(NAC

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

Pharmacological effects of nicotine (4)

A
  • Nicotine acts as an agonist of nAChRs
  • Produces physiological, behavioural, and subjective effects
  • The acute effects of nicotine differ from the chronic effects of nicotine
  • The effects of nicotine in the brain derive from the widespread distribution of the cholinergic system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Effects of nicotine on psychomotor function (4)

A
  • Nicotine’s behavioural effects include alterations in movement and cognitive function
  • Nicotine effects on psychomotor function differ between acute and chronic administration
  • Acute administration of nicotine induces a decrease in psychomotor activity
  • Chronic administration of nicotine results in an increase in psychomotor function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Effects of nicotine on cognitive function (5)

A
  • Nicotine shows some benefits for cognitive function
  • The effect of nicotine in alertness is circumstance- and dose- dependent
  • Nicotine has also been described to wake people up when they are drowsy and calms them down when they are tense
  • Small doses of nicotine tend to cause arousal, whereas large doses do the reverse
  • The effects on memory are unclear (placebo + not placebo results are similar)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cholinergic signalling: Drug targets (3)

A

-Vesamicol: drug targeting ACh v packaging

  • botulin (toxin): inhibits exocytosis
  • ACh esterase inhibitors: Alzheimer’s treatment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Muscarinic receptors signalling (2)

A

M1, M3, M5 = GQ/11 (excitatory)

M2, M4 = Gi/Go (inhibitory)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Muscarinic receptor locations (5)

A

M1: Neural (= CNS excitation, gastric secretion)

M2: Cardiac (= cardiac + neural inhib (tremors, hypothermia)

M3: Glandular/smooth muscle (= gastric/ salivary secretion, GI smooth muscle contraction, vasodilation)

M4: CNS (= enhanced locomotion)

M5: CNS but localised in SN, salivary glands, iris/ciliary muscle (=unknown)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Catecholamines synthesis (5)

A

1) L-Tyrosine
—Tyrosine Hydrolase—
2) L-dopa (parkinsons treatment)
— Dopa decarboxylase—
3) Dopamine
—Dopamine beta-hydroxylase—
4) Noradrenaline
—Phenylethanolamine N-methyltransferase—
5) Adrenaline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Dopamine pathways (4)

A

1) Nigrostriatal (SN -> striatum)
2) Mesolimbic (VTA -> NAcc)
3) Mesocortical (VTA -> DL, VM PF)
4)Tuberoinfundibular ( Hypo -> AP)

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

Dopamine receptors classification (6)

A

D1- like :
- D1, D5
- Large C-terminal domain
- Gs signalling

D2-like :
- D2, D4, D6
- large intracellular loop
- Gi signalling

= ST responses + gene transcription

20
Q

Adrenal medulla info (4)

A
  • Composed of modified postganglionic
    neurons
  • Stimulated by preganglionic fibres
  • Release 80% adrenaline, 20%
    noradrenaline (small amounts
    dopamine, neuropeptides and ATP)
  • Release their transmitters directly into the bloodstream
21
Q

Adrenoceptors subtypes + potency (3)

A
  • subtypes are α (a1 type + a2 type) and β
  • Potency at α receptors is noradrenaline > adrenaline > isoprenaline
  • Potency at β receptors is isoprenaline > adrenaline > noradrenaline

(NαI βrIAN)

22
Q

Adrenoceptor subtype signalling + response (3)

A

α1: Gq = smooth muscle
contraction (GI, Bladder, Skin vasocons.)

α2: Gi/o = smooth muscle
contraction - mixed effects, platelet activation

β1: Gs = Heart muscle contraction, smooth muscle relaxation, glycogenolysis
β2: Smooth muscle relaxation
β3: Enhance lipolysis, Relaxation of
detrusor muscle in the bladder

23
Q

Presynaptic agents/drugs (5)

A
  • alpha-methyldopa NA: hypertension treatment - specifically in pregnancy (acts as a false neurotransmitter = reduces adrenaline effects)
  • carbidopa alpha-methyldopa: prevents Dopa D carboxylase = no dopamine –> parkinsons so dopamine doesn’t cross BBB
  • cocaine, imipranine: works by building up in cleft
  • amphetamines, ephedrine: re-uptake + displace noradrenaline, build up = leaked in cleft

-clonidine, yohimbine:

24
Q

Catecholamine metabolism (2)

A

2 main enzymes:
- Monoamine oxidase => bound to mito
-Catecholemethyl transferase => adrenal medulla: regs signal of adrenaline

25
Q

Opioids def (1)

A

naturally occurring, synthetic or semi-synthetic
compounds which act at opioid receptors

26
Q

Naturally occurring compounds (also known as opiates) def (1)

A

usually derived from the resin of the opium poppy. Main egs alkaloids such as morphine, codeine and thebaine

27
Q

Morphine esters (1)

A

derived from opium- include morphine prodrugs such as diacetylmorphine (heroin)

28
Q

Semi-synthetic opioids (1)

A

derived from opium or morphine esters - include buprenorphine and oxycodone

29
Q

Synthetic opioids (1)

A

include fentanyl, pethidine, methadone and tramadol

30
Q

Endogenous opioids (1)

A

include enkephalins and endorphins

31
Q

Diacetylmorphine - heroin (2)

A
  • not an active drug but is rapidly metabolised into active drugs:
    1) heroin
    2) 6-monoacetylmorphine (active)/ 3-monoacetylmorphine (inactive)
    3) morphine (active)
  • 2 acetyl groups make the compound more lipid soluble = cross BBB much easier
32
Q

Opioid receptors (4)

A

mu - main
kappa
delta
NOP

all Gi/o

33
Q

opioids in pain pathway (5)

A

ascending pathway:
1) noxious stimulus
2) C-fibre activity
3) excitation of transmission neuron
4) output from brain = pain

opioids work on descending pathway (5-HT, NA –> reduce transmission of pain) and Ascending pathway (reduce activation of C-fibres

34
Q

Opioid abuse effects (8)

A

-have a very high abuse potential

-have been used and abused since antiquity – evidence suggests the opium poppy was cultivated as far back as 3400 B.C.

  • Surge of pleasurable sensation (“rush”)
  • Reduced stress and anxiety
  • Reduced pain (physical and psychological)
  • Sedation
  • Impaired mental function
  • Cardiac and respiratory function slows
    (can be life threatening)
35
Q

What reverses opioid overdose + how? (2)

A

naxolone reverses opioid overdose

by works as an opioid antagonist => higher affinity = decreases/reverses effects

36
Q

Why is fentanyl ~100 times more potent than morphine? (3)

A

Fentanyl is much more potent in vivo, but has similar binding and potency in vitro

fentanyl is much more lipophilic it can cross the BBB much easier than morphine

So, for an equivalent dose, much more fentanyl gets into the CNS
- More drug in the brain = more mu-opioid receptor activated = greater CNS effects
(e.g. respiratory depression via mu-opioid receptors in respiratory areas in the brain stem)

37
Q

β-arrestin 2 knockout mice do not develop anti-nociceptive morphine tolerance - experiment (3)

A
  • testing latency of rodent retracting tail from heat stimuli
  • more morphine = longer to retract tail
  • morphine for 9 days = tolerance
    -KO didnt develop tolerance
38
Q

Multiple molecular mechanisms may contribute to opioid tolerance (6)

A

1) Loss of MOR signalling
2) Accumulation of desensitised MOR
3) No change in endocytosis
3) Persistent PKC activity
4) GRK or arrestin increases desensitised MOR
5) Recycling is impaired

39
Q

Modulation of inhibitory synaptic transmission-experiment results - CB1 agonist + GABA (3)

A

CB1 agonists inhibit GABA-mediated synaptic transmission

1) CB1 agonist reduces postsynaptic sensitivity to GABA (postsynaptic effect)

2) CB1 agonist reduces presynaptic release probability (presynaptic effect)
* Reduces probability of action potential firing
* Inhibits release mechanisms
* Inhibits action-potential dependent Ca2+channel activity
* Inhibits action-potential independent Ca2+ channel activity

40
Q

Using miniature synaptic currents to determine synaptic locus of drug effect (3)

A
  • If amplitude (A) of events reduced → postsynaptic effect
  • If frequency (F) of events reduced → presynaptic effect
  • If no effect → presynaptic, action potential dependant
    effect
41
Q

Effect of CB1 agonists on miniature inhibitory postsynaptic currents (ISPC’s) (3)

A

CB1 agonists do NOT affect:
* mIPSC frequency
* mIPSC amplitude

But DO reduce evoked IPSCs

Therefore, they reduce AP dependant GABA release (via inhibition of Ca2+ channels)

42
Q

Depolarisation induced suppression of
inhibition (DSI) experiment (2)

A
  • Depolarisation of postsynaptic cell results in a transient reduction in GABAergic transmission
  • Observed in cellebellar Purkinje cells, medium spiny neurones of the striatum and hippocampal pyramidal cells etc.
43
Q

1) Evidence that DSI is mediated via a
retrograde messenger (5)

A

1) Increase in postsynaptic [Ca2+]i is necessary and sufficient for the induction of DSI

  • Blockers of Ca2+ entry block DSI
  • Postsynaptic Ca2+ chelating agents prevent DSI
  • Artificially raising [Ca2+] (uncaging) induces DSI
  1. The frequency (number) of spontaneous inhibitory
    synaptic events is reduced – fewer vesicles released
    presynaptically
  2. Postsynaptic sensitivity to exogenously applied GABA is not affected by depolarisation
44
Q

2) Evidence that DSI is mediated via a retrograde messenger (2)

A
  1. DSI is not blocked by classical neurotransmitter receptor antagonists
  2. DSI is not synapse or cell-specific
45
Q

DSI is mediated by endocannabinoids (6)

A

1.Synthesis and release of endocannabinoids dependent on Ca2+

2.CB1 agonists depress GABAergic transmission

3.DSI is blocked by the CB1 antagonists

4.DSI is mimicked by blocking endocannabinoid uptake

5.DSI is absent in the CB1 knockout mouse

Endocannabinoids are released in response to
postsynaptic depolarisation/action potentials →
suppression of GABA release

Molecular + Cellular Neuro (21 decks)

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