Fig. 1: Summary of cholinergic neurotransmission.

Acetylcholine is synthesized from choline and acetyl-coA by choline acetyltransferase, packed into vesicles by a vesicular acetylcholine transporter, and, after release, broken down by acetylcholinesterase. The effects of released acetylcholine are conveyed by nicotinic ligand-gated ion channels and muscarinic metabotropic (G-protein coupled) receptors. There are 5 muscarinic receptor subtypes: M1–M5. Muscarinic M2 receptors can act as pre-synaptic auto-receptors on cholinergic neurons, while the other subtypes act mainly as heteroreceptors on other cholinoceptive neuronal types (both pre- and post-synaptically). Nicotinic receptor subunits include α3, α4, α5, α6, α7, β2, and β4. The most common nicotinic receptors in the brain are the heteromeric α4β2 and the penta-homomeric α7 receptors, which are located both on cholinergic and cholinoceptive neurons (e.g., pre- and post-synaptically on dopamine neurons). Cortical and hippocampal innervation is primarily provided by projections from the basal forebrain and brainstem cholinergic nuclei, while the majority of acetylcholine release in the striatum is accounted for by cholinergic interneurons. Some evidence suggests that cholinergic neurotransmission also occurs by slow volume transmission across extracellular space, in addition to the classical synaptic transmission. Image created in BioRender.com.