Topic 5: Acetylcholine Receptors Flashcards
Where does cholinergic neurotransmission occur?
neuromuscular junctions: where motor neurons connect to muscle
CNS
autonomic nervous system (ANS): preganglionic neurons of the sympathetic and parasympathetic branch, ganglionic neurons of the parasympathetic branch
What are agonists of muscarinic receptors?
agonists of muscarinic receptors are parasympathomimetic, as they mimic effects of activation of the parasympathetic nervous system
mimics parasympathetic nervous system
What are antagonists of muscarinic receptors?
antagonists of muscarinic receptors are parasympatholytic, as they inhibit parasympathetic functions
What is the striatum?
involved in motor function
ACh balances out dopamine; if out of balance, Parkinson’s
ACh involved in motor function
What is the dorsolateral pons?
involved in arousal (reticular activating system) and addictions
What is the BFCS?
basal forebrain cholinergic system; learning, memory, and attention
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
What is atropine?
plant alkyloid found in the nightshade plant
antagonist of the muscarinic ACh receptor: blocker of receptor, inhibit parasympathetic function
administered opthalamologically to dilate pupils: parasympatholytic effect (inhibiting parasympathetic system)
BBB permeable
oral administration inhibits cognition in animals (acquisition and maintenance of learning tasks)
How does ACh in the BFCS impact cognition?
administration of atropine or the related scopolamine is amnesiac in humans
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 labor (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; we don’t remember because we aren’t paying attention to things
What was the microdialysis on ACh levels during attention?
using microdialysis researchers showed that ACh levels increased during tasks requiring sustained attention more so than comparative tasks
operant control task - reward task e.g. lever press for food reward
F19-s schedule of reinforcement - operant reward task with a predictable delay
only see drastic increase in ACh in attention task
What is saporin?
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)
What is 192-IGG saporin?
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
How does ACh interact with arousal systems?
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
How is ACh involved in addiction?
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
nicotine is an agonist to ACh acts on receptors within VTA
What are the two families of cholinergic receptors that 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)
What are nicotinic acetylcholine receptors?
NAChR are a family of ligand gated ion channels
permeable to Na+ and Ca2+
nicotine is a selective agonist of NAChR
found in neuromuscular junction, sympathetic, parasympathetic, and central nervous system
most popular agonist for this receptor is nicotine
