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Psych 478 > Acetylcholine Systems and Receptors > Flashcards

Acetylcholine Systems and Receptors Flashcards

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1
Q

Describe cholinergic neurotransmission

A
  • Neuromuscular junctions
  • CNS
  • Autonomic nervous system (ANS)
  • Preganglionic neurons of the sympathetic and parasympathetic
    branch
  • Ganglionic neurons of the parasympathetic branch
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2
Q

Describe fight or flight

A

Sympathetic ANS

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3
Q

Describe conservation and relaxation

A

Parasympathetic ANS

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4
Q

What are agonists of muscarinic receptors?

A

parasympathomimetic, as they mimic effects of activation of the parasympathetic nervous system

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5
Q

What are antagonists of muscarinic receptors?

A

parasympatholytic, as they inhibit parasympathetic functions

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6
Q

Describe the BCFS

A

basal forebrain cholinergic system Learning, memory, and attention

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7
Q

Describe the striatum

A

Involved in motor function

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8
Q

Describe dorsolateral pons

A

Involved in arousal (reticular activating system) and addictions

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9
Q

What is the BCFS?

A
  • Cholinergic neurons located in medial septum, diagonal band nuclei, nucleus basalis, and substantia innominate
  • Projections to cortex, hippocampus, amygdala
  • Loss of BFCS cholinergic neurons is associated with cognitive
    decline in Alzheimer’s disease
  • Implicated in memory and attention
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10
Q

What is atropine?

A
  • Plant alkyloid found in the nightshade plant
  • Antagonist of the muscarinic Ach receptor
  • Administered opthalamologically to dilate pupils
  • Parasympatholytic effect (inhibiting
    parasympathetic system)
  • BBB permeable
  • Oral administration inhibits cognition in animals (acquisition and maintenance of learning tasks)
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11
Q

Describe the role of ACH and the BCFS in cognition

A
  • Administrationofatropineortherelatedscopolamineisamnesiacinhumans
  • Scopolamine and morphine was a drug combination often administered during labour in the early- mid 20th CE
  • Scopolamine induces a ‘twilight sleep’ avoiding both the pain and memory of labour (discontinued due to adverse effects on newborns)
  • ACh thought to be important for memory consolidation (esp. episodic) due to innervation of the hippocampus
  • Alternately proposed to affect memory through effects on attention and sensory discrimination
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12
Q

What did micro dialysis research show?

A

Using microdialysis researchers showed that ACh levels increased during tasks requiring sustained attention more so than comparative tasks.

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13
Q

What is the operant control task?

A

reward task e.g. lever press for food reward

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14
Q

What is a FI9-s schedule of reinforcement?

A

operant reward task with a predictable delay

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15
Q

Describe saporin

A

Protein toxin isolated from soapwort plant
(Saponaria officinalis)

Water soluble toxin

Highly specific inhibitor of ribosome function (ribosome inactivating protein – RIP)

Can be conjugated to antibodies to target specific cell types (investigated as anti-cancer agent)

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16
Q

Describe 192-IGG SAPORIN

A

Conjugated to an antibody that targets basal forebrain cholinergic neurons

Administration to ventricular system results in targeting of BFCS neurons and selective lesion of only the cholinergic cells

BFCS lesion produces specific deficits in learning, memory (esp. spatial), and attention

  • In sustained attention tasks animals lesioned with 192 IgG-saporin had a lower number of correct hits when the signal strength was weak suggesting deficits in attention.
  • Performance was comparable on other aspects of the task, suggesting no global cognitive or motor impairment.
17
Q

Describe arousal systems

A
  • ACh is one component of the reticular activating system
  • Cholinergic projections from the pons (pedunculopontine nucleus and laterodorsal tegmental nucleus) are active while awake and trigger the transition to REM sleep
  • Reticular activation also involved in increasing attention
18
Q

Describe addictions

A

Cholinergic neurons originating in the dorsolateral pons innervate the ventral tegmental area.

ACh stimulates dopaminergic neurons projecting to the nucleus accumbens (reward circuitry).

Nicotine activates nicotinic ACh receptors to directly activate dopaminergic neurons in the VTA.

19
Q

Describe acetylcholine receptors

A
  • Two families of cholinergic receptors are found in mammals
  • Nicotinic receptors (NAChR)
  • 17 varieties
  • Ionotropic receptors pass Na+ and Ca2+
  • Muscarinic receptors (MAChR)
  • 5 varieties
  • Metabotropic receptors (G-protein coupled receptors)
20
Q

What are nACHrs?

A
  • NAChR are a family of ligand gated ion channels
  • Permeable to Na+ and Ca2+
  • Nicotine is a selective agonist of
    NAChR
  • Found at neuromuscular junction, sympathetic, parasympathetic, and central nervous system
21
Q

Describe depolarization blocks

A

NAChR desensitize (inactivate in the presence of a prolonged stimulus)

Agonists that do not readily desensitize receptors cause a depolarization block (preventing the target cell from firing by preventing repolarization)

Succinylcholine is a muscle relaxant that causes prolonged activation of NAChR and subsequent muscle paralysis

22
Q

Describe the functions of nicotinic receptors

A
  • At the neuromuscular junction NAChR are always located post-synaptically (classic transmission)
  • In the CNS NAChR can be located in both post- or pre-synaptic membranes
  • Pre-synaptic NAChR function to modulate neurotransmitter release – multiple types of
    neurons
  • NAChR antagonists include curare poision (D-tubocurarine)
  • Numerous tropical plants indigenous to S. America
  • Used as an arrow poison for hunting (causes respiratory paralysis)
23
Q

Describe ACh in invertebrates

A
  • ACh is a major neurotransmitter in insects
  • Neuronal NAChR have wide expression but different composition and sensitivity than in mammals
  • Neonicotinoidinsecticidesarebroad spectrum insecticides that have low adverse effects in mammals (selectivity and BBB impermeable)
  • Irreversible NAChR antagonists
24
Q

Describe MUSCARINIC ACETYLCHOLINE RECEPTORS

A
  • 5 types (M1 through M5 receptors)
  • All are metabotropic receptors (G-protein coupled receptors)
  • Specific agonist muscarine isolated from the fly agaric mushroom (Amanita muscaria)
  • Muscarine is parasympathomimetic
  • Ingestion leads to exaggerated parasympathetic
    response
  • Lacrimation, sweating, salivation, pinpoint pupils, severe abdominal pain (strong contraction of smooth muscles and painful diarrhea)
  • High doses – cardiovascular collapse, convulsions, coma, death
25
Q

Describe GPCRs

A
  • 7-transmembrane helix receptor family
  • Coupled to specific GTP binding protein on the intracellular side
  • Gs α – stimulates downstream targets
  • Gi α – inhibits downstream targets
  • Gq α – modulatory functions
    downstream
  • Elicit effects on target cells through second messengers
  • cAMP,IP3,Ca2+
26
Q

What does GPCR do?

A

binds ligand, interacts with G-protein complex

27
Q

What does the G protein complex do?

A

Gα binds GDP, Gβ-γ

28
Q

What does ligand binding do?

A

Ligand binding promotes dissociation of
Gα from Gβ-γ

29
Q

What does G alpha do?

A

Newly liberated Gα activates downstream effector (e.g. adenylate cyclase → generates cAMP)

30
Q

What does Gβ-γ do?

A

Gβ-γ can similarly bind and act on other effectors

31
Q

Describe the GQΑ /PLC SIGNALLING C ASC ADE

A

PLC activation cleaves PIP2 (membrane phospholipid) to IP3 (soluble) and DAG (lipid)

IP3 activates Ca2+ channels on the ER to trigger Ca2+-release into the cytoplasm

DAG activates protein kinase C in conjunction with Ca2+

PKC phorphorylates numerous cellular proteins

32
Q

Describe G-PROTEIN COUPLING OF MUSCARINIC RECEPTORS

A
  • M1, 3, 5 → Gqα → phospholipase C → IP3 and Ca2+ release
  • M1 involved in neurotransmission in autonomic ganglion cells (both
    sympathetic and parasympathetic) and cognitive effects in CNS * M5 involved in addictive behaviour
  • M2, 4 → Giα → inhibits adenylate cyclase ↓ cAMP levels
  • M2 expressed in heart – activation slows heart rate
  • M4 functions as an autoreceptor – activation inhibits presynaptic ACh release
33
Q

Describe ACH in Parkinsons

A
  • ACh and dopamine in the striatum are in balance to regulate movement
  • Degeneration of dopaminergic neurons in the substantia nigra (nigrostriatal system) results in deficits in initiation of movement
  • Cholinergic drugs are used in early PD to treat motor symptoms
  • Orphenadrine (muscarinic M4 ACh receptor antagonist)
  • Manipulation of ACh in the striatum offsets the deficit in dopamine
34
Q

What is Latrotoxin?

A

(Black widow venom) – triggers ACh release

35
Q

Describe Botulinum toxin

A

Blocks ACh release

Psych 478 (28 decks)

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