The Response Dynamics and Function of Cholinergic and GABAergic Neurons in the Basal Forebrain During Olfactory Learning

Abstract

Modulation of neural circuits is essential for flexible sensory perception and decision-making in a changing environment. Cholinergic and GABAergic projections to the olfactory system from the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain are crucial for odor detection and olfactory learning. Although studies have demonstrated that HDB neurons respond during olfactory learning, how cholinergic and GABAergic neurons differ in their response dynamics and roles in olfactory learning remains unclear. In this study, we examined the response profiles of these two subpopulations of neurons during passive odor exposure and associative olfactory learning. We show that the excitatory responses in both cholinergic and GABAergic neurons tended to habituate during repeated passive odor exposure. However, while these habituated responses were also observed in GABAergic neurons during a go-go task, there was no such habituation in cholinergic neurons. Moreover, the responses to S+ and S- trials diverged in cholinergic neurons once mice learned a go/no-go task. Furthermore, the chemogenetic inactivation of cholinergic neurons in the HDB impaired odor discrimination. Together, these findings suggest that cholinergic neurons in the HDB reflect attention to positive reinforcement and may regulate odor discrimination via top-down inputs to the olfactory system.

Keywords: GABAergic neuron; basal forebrain; cholinergic neuron; fiber photometry; go/no-go.