Cholinergic circuit modulation through differential recruitment of neocortical interneuron types during behaviour.

Acetylcholine is a crucial neuromodulator for attention, learning and memory. Release of acetylcholine in primary sensory cortex enhances processing of sensory stimuli, and many in vitro studies have pinpointed cellular mechanisms that could mediate this effect. In contrast, how cholinergic modulation shapes the function of intact circuits during behaviour is only beginning to emerge. Here we review recent data on the recruitment of identified interneuron types in neocortex by cholinergic signalling, obtained with a combination of genetic targeting of cell types, two-photon imaging and optogenetics. These results suggest that acetylcholine release during basal forebrain stimulation, and during physiological recruitment of the basal forebrain, can strongly and rapidly influence the firing of neocortical interneurons. In contrast to the traditional view of neuromodulation as a relatively slow process, cholinergic signalling can thus rapidly convey time-locked information to neocortex about the behavioural state of the animal and the occurrence of salient sensory stimuli. Importantly, these effects strongly depend on interneuron type, and different interneuron types in turn control distinct aspects of circuit function. One prominent effect of phasic acetylcholine release is disinhibition of pyramidal neurons, which can facilitate sensory processing and associative learning.