Oscillatory Network Activity in the Accessory Olfactory Pathway: Mechanistic Basis and Functional Implications

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For mammals, chemosensation is an essential sensory modality. Its importance is underscored by the existence of multiple chemosensory subsystems. Of these, the vomeronasal system (VNS) is specifically associated with social and other innate behaviors. The first brain region of the VNS is the accessory olfactory bulb (AOB). Although the AOB shares gross similarities with its main olfactory system counterpart, there are major differences between the structures. Thus, extrapolation of physiological principles from the main olfactory bulb to the AOB, downplays the unique features of AOB physiology. Some of the most prominent features of VNS signaling involve its temporal dimension. Specifically, stimulus exposure, sensory processing, and the time scales of downstream targets are all significantly slower compared to other sensory systems. In the main olfactory system, activity is tightly coupled to breathing, exerting strong impact on sensory processing. By contrast, vomeronasal neurons are isolated from the breathing cycle. Yet, the absence of direct respiration-linked inputs to the VNS does not mean that oscillatory activity is not important in this system. Indeed, this proposal is based on two recent discoveries from our own laboratories which indicate that oscillations are present, prominent, and likely an integral feature of VNS function. At present, the specific roles of time and oscillations in VNS function still remains unclear. In fact, we still lack a basic functional and phenomenological understanding of the temporal aspects of AOB processing. In particular, very little is known about how the unique biophysical properties of the principal neurons of this structure, AOB mitral cells (AMCs) impact their response profiles, how their local network interactions shape AOB information processing, and how spontaneous and evoked AMC activity affects sensory representations. The focus of the current proposal is the largely unexplored temporal signature of chemosensory signaling in the AOB, with an emphasis on the role of AMCs.Our study is organized into three aims, each of which involves both in vitro and in vivo approaches, and hence requires close collaboration between both our groups. First, we will analyze the cellular and network mechanisms underlying spontaneous formation of oscillating microcircuits in the idle state. Second, we will study how these oscillations are modulated by sensory stimulation and by top-down inputs. Third, we will investigate both the role of LFP patterns in AOB information processing and the mechanisms underlying them. In a broader context, our experiments are motivated not only by our shared interest in the functional impact of oscillations on information processing within the AOB, but also on their effects on target nuclei in the amygdala and hypothalamus. Although the latter are beyond the scope of the current proposal, they guide us as topics for our future studies.