The role of the basal forebrain in associative learning

The basal forebrain (BF) 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. Intermingled with the cholinergic system, the BF also provides a parallel, equally widespread GABAergic projection of largely unknown function. Here we recorded different cell types of the mouse BF in associative learn ing paradigms. 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. PV-expressing GABAergic neurons showed tonic, sustained responses starting already after the predictive cues and outlasting cholinergic activation. These results suggest that cholinergic neurons form a rapid, reliable and temporally precise signaling route for reinforcement feedback, which may be specifically enhanced or enabled by disinhibition mediated by BF GABAergic projections. FINANCIAL SUPPORT: This work was supported by the “Lendület” Program of the Hungarian Academy of Sciences (LP2015-2/2015), ERC StG 715043, grants from the John Merck and McKnight Foundations, National Institute of Neurological Disorders and Stroke (R01NS075531), Swartz Foundation, Marie Curie International Outgoing Fellowship within the EU Seventh Framework Programme for Research and Technological Development.