Cellular and functional heterogeneity of interhemispheric connections in the anterior olfactory nucleus

ABSTRACT The olfactory system in most mammals begins with two unique air flows separated by a nasal septum. This allows the olfactory epithelium contained in each nostril to receive odorant information independently from the other. The mechanisms by which the brain combines these separate inputs to obtain perceptual unity remain unknown. Given the lack of interhemispheric connections within the primary olfactory area, the olfactory bulb, the combination of the lateralized input must lie within the olfactory cortex. The anterior olfactory nucleus (AON) is the earliest olfactory cortical area to project interhemispherically, making it an excellent candidate for the combination of bilateral olfactory information. As a primary sensory area that receives cortical input, the AON is implicated in social behavior and olfactory memory. Signaling between the hemispheres of the AON is necessary for some AON-dependent behaviors. However, the specific cell types involved in the interhemispheric AON connection are unknown, as well as the functional changes within the AON that result from contralateral input. Identifying the underlying circuitry within the AON is critical to understanding its role in the olfactory cortex and olfactory-dependent behaviors. Therefore, I will identify the cell types that send and receive interhemispheric projections in the AON through viral tracing. This will allow me to not only visualize the interhemispheric connections but to assess the density of such connections in the various AON subregions. I will further investigate the molecular identity of contralaterally-projecting AON neurons through single-nucleus RNA sequencing. This will not only generate genetic markers of interhemispherically-projecting neurons but serve as a resource for further study into the molecular diversity of the AON. To probe the functionality of the AON→AON connection, I will assess the neuronal activity resulting from the stimulation of contralaterally-projecting axons on the AON through in vitro whole-cell electrophysiology. Additionally, I will compare the response of the AON to ipsilateral and contralateral olfactory bulb stimulation in vivo. The combination of in vitro and in vivo electrophysiology will describe the synaptic currents resulting from the interhemispheric connection as well as the role of interhemispheric connection in the AON’s response to physiologically relevant stimuli. This work will contribute not just to our understanding of the AON, but also to the processing and computation done by the olfactory cortex. Insights from the cellular and functional diversity within the AON will guide future research on the role of the AON in olfactory-related disorders.