Centrifugal Inputs to the Main Olfactory Bulb Revealed Through Whole Brain Circuit-Mapping

Neuronal activity in sensory regions can be modulated by attention, behavioral state, motor output, learning, and memory. This is often done through direct feedback or centrifugal projections originating from higher processing areas. Though, functionally important, the identity and organization of these feedback connections remain poorly characterized. Using a retrograde monosynaptic g-deleted rabies virus and whole-brain reconstructions, we identified the organization of feedback projecting neurons to the main olfactory bulb of the mouse. In addition to previously described projections from regions such as the Anterior Olfactory Nucleus (AON) and the piriform cortex, we characterized direct projections from pyramidal cells in the ventral CA1 region of hippocampus and the entorhinal cortex to the granule cell layer (GCL) of the main olfactory bulb (MOB). These data suggest that areas involved in stress, anxiety, learning and memory are all tethered to olfactory coding, two synapses away from where chemical compounds are first detected. Consequently, we hypothesize that understanding olfactory perception, even at the earliest stages, may require studying memory and behavior in addition to studying the physiochemical features of odors.