Abstract:

The nucleus basalis (NB) gives rise to the central cholinergic neuromodulatory system that innervates the entire neocortex and is thought to regulate sensory processing, attention and learning. However, it is not known when cholinergic neurons are recruited during behavior and how their activity might support different aspects of cognition. We used optogenetic identification to record cholinergic neurons in behaving mice. Central cholinergic neurons were characterized as bursting and non-bursting cells. We found that both subtypes responded phasically to primary reward and punishment with remarkable speed and precision (18±2 ms), unexpected for a neuromodulatory system. Responses to reward were scaled by reinforcement surprise, raising the possibility that the cholinergic system also conveys cognitive information. Tonic firing properties changed during sleep-wake states but remained similar for bursting and non-bursting neurons, contradicting the current view of bursting cells transmitting phasic information and tonic, non-bursting neurons setting ambient acetylcholine levels. These results suggest that cholinergic neurons form a rapid, reliable and temporally precise signaling route for reinforcement feedback that can mediate fast cortical activation and plasticity.