Acetylcholine modulates cortical synaptic transmission via different muscarinic receptors, as studied with receptor knockout mice.

The central cholinergic system plays a crucial role in synaptic plasticity and spatial attention; however, the roles of the individual cholinergic receptors involved in these activities are not well understood at present. In the present study, we show that acetylcholine (ACh) can facilitate or depress synaptic transmission in occipital slices of mouse visual cortex. The precise nature of the ACh effects depends on the ACh concentration, and is input specific, as shown by stimulating different synaptic pathways. Pharmacological blockade of muscarinic receptor (mAChR) subtypes and the use of M1-M5 mAChR-deficient mice showed that specific mAChR subtypes, together with the activity of the cholinesterases (ChEs), mediate facilitation or depression of synaptic transmission. The present data suggest that local ACh, acting through mAChRs, regulates the cortical dynamics making cortical circuits respond to specific stimuli.