Dynamic Impairment of Olfactory Behavior and Signaling Mediated by an Olfactory Corticofugal System.

Processing of olfactory information is modulated by centrifugal projections from cortical areas, yet their behavioral relevance and underlying neural mechanisms remain unclear in most cases. The anterior olfactory nucleus (AON) is part of the olfactory cortex, and its extensive connections to multiple upstream and downstream brain centers place it in a prime position to modulate early sensory information in the olfactory system. Here, we show that optogenetic activation of AON neurons in awake male and female mice was not perceived as an odorant equivalent cue. However, AON activation during odorant presentation reliably suppressed behavioral odor responses. This AON-mediated effect was fast and constant across odors and concentrations. Likewise, activation of glutamatergic AON projections to the olfactory bulb (OB) transiently inhibited the excitability of mitral/tufted cells (MTCs) that relay olfactory input to the cortex. Single-unit MTC recordings revealed that optogenetic activation of glutamatergic AON terminals in the OB transiently decreased sensory-evoked MTC spiking, regardless of the strength or polarity of the sensory response. The reduction in MTC firing during optogenetic stimulation was confirmed in recordings in awake mice. These findings suggest that glutamatergic AON projections to the OB impede early olfactory signaling by inhibiting OB output neurons, thereby dynamically gating sensory throughput to the cortex. [ABSTRACT FROM AUTHOR]