Abstract
Processing of sensory information is substantially shaped by centrifugal, or feedback, projections from higher cortical areas, yet the functional properties of these projections are poorly characterized. Here, we used genetically-encoded calcium sensors (GCaMPs) to functionally image activation of centrifugal projections targeting the olfactory bulb (OB). The OB receives massive centrifugal input from cortical areas but there has been as yet no characterization of their activity in vivo. We focused on projections to the OB from the anterior olfactory nucleus (AON), a major source of cortical feedback to the OB. We expressed GCaMP selectively in AON projection neurons using a mouse line expressing Cre recombinase (Cre) in these neurons and Cre-dependent viral vectors injected into AON, allowing us to image GCaMP fluorescence signals from their axon terminals in the OB. Electrical stimulation of AON evoked large fluorescence signals that could be imaged from the dorsal OB surface in vivo. Surprisingly, odorants also evoked large signals that were transient and coupled to odorant inhalation both in the anesthetized and awake mouse, suggesting that feedback from AON to the OB is rapid and robust across different brain states. The strength of AON feedback signals increased during wakefulness, suggesting a state-dependent modulation of cortical feedback to the OB. Two-photon GCaMP imaging revealed that different odorants activated different subsets of centrifugal AON axons and could elicit both excitation and suppression in different axons, indicating a surprising richness in the representation of odor information by cortical feedback to the OB. Finally, we found that activating neuromodulatory centers such as basal forebrain drove AON inputs to the OB independent of odorant stimulation. Our results point to the AON as a multifunctional cortical area that provides ongoing feedback to the OB and also serves as a descending relay for other neuromodulatory systems.
Highlights
Sensory systems enable an animal to detect and act upon relevant environmental information in order to navigate and survive in a complex world
Stereotaxic injection of the Cre-dependent viral vectors rAAV 2/1.FLEX.GCaMP3 (Atasoy et al, 2008; Tian et al, 2009; Betley and Sternson, 2011) or rAAV2/9.FLEX.GCaMP6s (Chen et al, 2013) centrally into the anterior olfactory nucleus (AON) resulted in strong genetically-encoded calcium reporters (GCaMPs) expression in principal neurons in all major AON subdivisions
Olfactory cortex sends strong feedback projections to the olfactory bulb (OB), the first stage of synaptic processing in the olfactory system. While this cortical feedback has been shown to profoundly modulate OB output and hypothesized to play an integral role in olfactory processing in the awake animal (Strowbridge, 2009; Boyd et al, 2012; Markopoulos et al, 2012; Soria-Gómez et al, 2014), the functional properties of feedback to the OB from any neuronal population have yet to be characterized in vivo
Summary
Sensory systems enable an animal to detect and act upon relevant environmental information in order to navigate and survive in a complex world. Numerous studies have investigated the modulation of activity in the olfactory bulb (OB)—the first stage of synaptic processing of olfactory sensory input—as a function of behavioral state and found rapid and profound effects (Karpov, 1980; Kay and Laurent, 1999; Doucette and Restrepo, 2008; Kato et al, 2012; Wachowiak et al, 2013; Nunez-Parra et al, 2014). It has been hypothesized that centrifugal modulation from diverse brain centers plays an important role in mediating these effects (Matsutani and Yamamoto, 2008; Shea et al, 2008; Petzold et al, 2009; Nunez-Parra et al, 2013; Rothermel et al, 2014).
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