Cell type-specific basal forebrain GABAergic neuronal activity with olfactory task performance, learning, and decision-making

Abstract

AbstractSensory perception relies on the flexible detection and interpretation of stimuli across variable contexts, conditions, and behavioral states. The basal forebrain is a hub for behavioral state regulation, supplying dense cholinergic and GABAergic projections to various brain regions involved in sensory processing. Of GABAergic neurons in the basal forebrain, parvalbumin (PV) and somatostatin (SST) subtypes serve opposing roles regulating behavioral states. To elucidate the role of basal forebrain circuits in sensory-guided behavior, we investigated GABAergic signaling dynamics during odor-guided decision-making. We used fiber photometry to record cell type-specific basal forebrain activity during an odor discrimination task and correlate temporal patterns of PV and SST neuronal activity with olfactory task performance. We found that PV-expressing GABAergic neurons are activated by odors and are selectively suppressed by reward. However, SST-expressing GABAergic neurons are activated during both odor and reward delivery. Notably, odor and reward responses of PV and SST neurons are uniquely correlated with behavioral measures of odor discrimination and decision bias. Additionally, as mice undergo discrimination learning, the magnitude of reward-related excitation decreases in SST neurons, while reward-related suppression increases in PV neurons. Finally, we show that chemogenetic inhibition of SST neurons alters decision bias to favor reward-seeking. These results suggest that subtypes of GABAergic basal forebrain neurons are differentially involved in decision-making, and that their bidirectional activity impacts decision making during olfactory guided behavior.