Abstract
Cortical sensory areas send excitatory projections back to earlier stage of sensory processing. Here, we uncover for the first time the existence of a corticofugal inhibitory feedback between two sensory areas, paralleling the well-documented excitatory feedback. In the olfactory system, we reveal that a subpopulation of GABAergic neurons in the anterior olfactory nucleus and anterior piriform cortex target the olfactory bulb. These long-range inhibitory inputs synapse with both local and output olfactory bulb neurons, mitral and tufted cells. Optogenetic stimulation coupled to in vivo imaging and network modeling showed that activation these inhibitory inputs drives a net subtractive inhibition of both spontaneous and odor-evoked activity in local as well as mitral and tufted cells. Further, cortical GABAergic feedback stimulation enhanced separation of population odor responses in tufted cells, but not mitral cells. Targeted pharmacogenetic silencing of cortical GABAergic axon terminals in the OB impaired discrimination of similar odor mixtures. We propose here that cortical GABAergic feedback represents a new circuit motif in sensory systems, involved in refining sensory processing and perception.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵# Jointly supervised this work
New data: -Control experiments: validation of the Cre-dependent tools (Supplemental Fig. 1), validation of the GABAergic nature of the light-evoked currents (Figure 3), validation of the cell quantification (Supplemental Figure 1 and 3) -Additional molecular and axonal projection characterization (Figure 2 and Supplemental Figure 1) -Rabies-tracing data showing direct inputs on MCs/TCs (Supplemental Fig 5) -Slice recordings from TCs (Figure 3) -A theoretical model that recapitulates and validates our experimental findings (Figure 5)