acetylcholine synthesis
One-step reaction
Choline (from diet) + Acetyl-CoA (from cell metabolism) → ACh
acetylcholine release
Action potential arrives
Calcium enters the terminal
Vesicles fuse with the membrane
ACh is released into the synaptic cleft
acetylcholine inactivation
ACh → (AChE) → choline + acetate
choline → reuptake → new ACh synthesis
AChE (acetylcholinesterase) binds ACh
↓
AChE breaks ACh into:
* Choline
* Acetic acid
↓
Choline is transported back into presynaptic neuron
(via high-affinity choline transporter, blocked by HC-3)
↓
Recycled choline used by ChAT to make new ACh
organization of the cholinergic system
- Peripheral Cholinergic Pathways
- Neuromuscular Junction
- Autonomic Nervous System
a) Preganglionic neurons pns and sns
b) Postganglionic parasympathetic neurons
2) Central (Brain) Cholinergic Pathways
- Striatal Cholinergic Interneurons
- Basal Forebrain Cholinergic System (BFCS)
- Brainstem Cholinergic System (LDTg & PPTg)
The cholinergic system is organized into peripheral and central components.
In the PNS, ACh is used at the neuromuscular junction and in both sympathetic and parasympathetic ganglia (with parasympathetic postganglionic neurons also using ACh).
In the CNS, cholinergic neurons are grouped into three major systems: striatal interneurons, the basal forebrain cholinergic system, and the brainstem tegmental system.
function of the cholinergic system
- Motor Control (Somatic Nervous System – PNS)
- Autonomic Regulation (PNS – Sympathetic & Parasympathetic)
- Cognitive Function (CNS – Basal Forebrain System)
- Behavioral State Regulation (CNS – Brainstem Cholinergic System)
- Motor Modulation in the Striatum (CNS)
The cholinergic system controls muscle movement, autonomic functions, attention and memory, sleep and arousal, and motor regulation. Dysfunction contributes to disorders like Alzheimer’s disease and Parkinson’s disease.
major subtypes of acetylcholine Receptors (2)
1) Nicotinic Receptors (nAChRs) ionotropic, fast, excitatory
- Muscle Nicotinic Receptors
- Neuronal Nicotinic Receptors
2) Muscarinic Receptors (mAChRs) metabotropic, slow, modulatory
- Excitatory odd numbed M1.M3,M5
- Inhibitory even M2, M4
anatomy of the cholinergic pathways
BFCS → cortex + hippocampus (attention, memory)
Striatal interneurons → regulate movement (Parkinson’s link)
PPTg/LDTg → VTA for reward and REM sleep
Preganglionic neurons → ACh → nicotinic
Parasympathetic postganglionic → ACh → muscarinic
Cholinergic neurons originate from specific nuclei and project to defined targets.
The basal forebrain system (nucleus basalis, medial septum, diagonal band) sends dense cholinergic projections to the cortex, hippocampus, and amygdala to support memory and attention.
Striatal cholinergic interneurons are local circuit neurons that modulate dopaminergic input and motor control.
The PPTg and LDTg send ascending cholinergic projections to the thalamus and VTA (affecting arousal and reward) and descending projections to the spinal cord involved in REM sleep initiation.
Acetylcholine is a neurotransmitter that has key functions where?
in the brain and
at the neuromuscular junction.
Cholinergic motor neurons in the spinal cord are characteristically positive for which enzyme?
ChAT
Acetylcholine is
PNS neurotransmitter
in the:
- neuromuscular junction (motor neurons)
-parasympathetic synapses
- some sympathetic synapses
Acetylcholine regulation
- availability
More choline = more ACh
More acetyl-CoA = more ACh - Neuronal firing rate
Higher firing = more ACh synthesized + released - Transporters
VAChT controls how much ACh is put into vesicles - Feedback mechanisms
ACh does not have autoreceptors has presynaptic nicotinic receptors that modulate release. - Drugs/toxins
Black widow venom → increases release
Botulinum toxin → blocks release
Vesamicol → reduces vesicle loading
Summary of the cholinergic pathways
Cholinergic pathways include peripheral systems (neuromuscular junction and autonomic ganglia) and three major central pathways: striatal interneurons for motor control, basal forebrain projections for learning and attention, and brainstem tegmental nuclei involved in REM sleep, arousal, and dopamine-mediated reward.
What drug overstimulates muscle nAChRs to cause depolarization block?
Succinylcholine (muscle paralytic).
What drug blocks muscle nicotinic receptors to cause paralysis?
d-tubocurarine (curare).
What is nicotinic receptor desensitization?
Prolonged ACh/nicotine exposure → receptor enters a state where it cannot open.
What is depolarization block?
Persistent activation causes loss of resting potential → cell cannot fire.
What are the excitatory muscarinic receptors?
M1, M3, M5 — activate phosphoinositide pathway (Gq).
What are the inhibitory muscarinic receptors?
M2, M4 — decrease cAMP (Gi) and open K⁺ channels.
Where is M1 mainly located?
Cortex & hippocampus — cognition and memory.
What does M2 do in the heart?
Slows heart rate (parasympathetic effect).
What does M3 control?
Smooth muscle contraction and glandular secretion (sweat, saliva).
What unique area expresses M5 receptors?
VTA dopamine neurons (drug reward & reinforcement).
What do M2/M4 autoreceptors do?
Inhibit ACh release from cholinergic terminals.
What makes nicotinic receptors unique compared to muscarinic?
They are ionotropic, fast, and can cause depolarization block.
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Unit 131
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Unit 228
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Unit 322
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Unit 414
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Unit 575
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Unit 654
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Unit 736
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Unit 845
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Unit 9 Addiction27
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Unit 10 Alcohol22
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Unit 11 Opioids13
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Unit 12 Psychomotor Stimulants21
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Unit 13 Caffiene Nicotine49
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Unit 14 Cannibis62
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Unit 15 Psychedelics60
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Unit 16 Inhalants Ghb Asa45
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Unit 17 Anxiety86
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Unit 18 Affective Disorders60
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Unit 19 Schizophrenia61
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Unit 20 Neurodegenerative Conditions43
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Definitions All Units203
