Cortical Feedback Control of Olfactory Bulb Circuits

Cortical feedback is a universal feature of all sensory systems, and represents an important general strategy for optimizing sensory encoding. The primary olfactory, or piriform, cortex (PCx) sends dense feedback projections to the olfactory bulb (OB) which can modulate incoming sensory information. Previous work has illuminated many details regarding the ascending pathway by which mammalian olfactory circuits encode odors; however information regarding the anatomy and function of the complementary descending feedback pathways remains rudimentary. Here we use optogenetic activation of cortical feedback projection (CFP) axons in order to establish their postsynaptic targets in mouse acute OB slices. We find that CFPs target a diverse array of GABAergic interneurons in the OB, and ultimately drive disynaptic inhibition of mitral and tufted (M/T) cells via monosynaptic excitation of inhibitory granule (GC) and periglomerular (PG) cells. In vivo activation of PCx suppresses odor evoked M/T cell activity, and enhances odor evoked inhibition. Together, these results suggest that PCx can gate OB output, and thus control the gain of its own input. We subsequently sought to characterize CFPs via 2-photon calcium imaging of feedback axons in the OB of awake mice. We find that odor-evoked activity in CFPs is diverse, with some axons displaying high odor selectivity while others are broadly tuned. We further observe that anesthesia reduces the frequency, amplitude, and duration of odor evoked cortical feedback excitation. In the OB, glomeruli form a spatially stereotyped map of odor molecular features. In contrast, in PCx odors activate dispersed ensembles of pyramidal cells lacking spatial topography, raising the question of whether CFPs have functional organization matching that of their postsynaptic targets in OB or retain the dispersed organization of PCx. We addressed this question via intrinsic optical imaging to map the odor evoked activation of OB glomeruli and calcium imaging of CFPs underlying identified glomeruli. Our results suggest that cortical inputs tuned to different odors are spatially interspersed and target individual glomerular channels diffusely and indiscriminately. This work establishes the circuitry of cortical feedback projections in the mammalian olfactory system, and demonstrates a functional role for PCx feedback in driving inhibition of OB outpu