Modulation of early olfactory circuits by long-range GABAergic inhibition

Abstract

Sensory perception emerges from the interplay between stimulus-driven feedforward cortical activation and feedback signals that sculpt the activity of early sensory circuits. Odor information is first processed in the olfactory bulb and the activity of its circuits is flexibly shaped by descending signals that arise in several brain regions, including neurons in the basal forebrain (BF). Among these neurons, a group of GABAergic neurons in the BF can modulate odor processing, however, how is this achieved is unknown. Here, we investigate how the activity of long-range GABAergic neurons in the BF modulate the spatiotemporal dynamics of the bulb output neurons. To examine the odor evoked responses of GABAergic neurons, we monitor the activity of their axons in the olfactory bulb of awake mice and characterize their response as a function of odor identity and concentration, using multiphoton calcium imaging. In addition, we provide anatomical and functional evidence for the existence of a feedback loop that is able to recruit GABAergic neurons in the BF through direct glutamatergic inputs originating in the olfactory cortex. Our work underscores basic principles on how stimulus-driven feedforward information recruits higher-order brain regions to provide descending feedback signals capable of shaping the output of early sensory processing stages.