Olfactory Coding in Ventral CA1 Region of the Hippocampus - PROJECT SUMMARY/ABSTRACT Olfaction is an evolutionarily conserved sensory system, and olfactory cues uniquely interact with limbic functions including memory and emotion in healthy individuals. Deficits in olfaction are a common finding in multiple neurodegenerative diseases that also disrupt memory and emotion. However, the mechanisms underlying these olfactory deficits, as well as those underlying normal olfactory-limbic functions, are unknown. Previous studies show that strong reciprocal anatomical connections link primary olfactory brain regions, including the posterior piriform cortex (pPIR) to limbic structures, including the ventral CA1 region of the hippocampus (vCA1). vCA1 is connected to primary olfactory brain regions via polysynaptic connections through the entorhinal cortex, but recent studies have also established monosynaptic projections to vCA1 directly from pPIR, which may provide another feedforward route by which olfactory information can reach vCA1. The structure of these connections and their role in encoding and integrating olfactory information remain poorly understood. Additionally, while odorant-tuning has been previously reported in dorsal hippocampal neurons, odor responses in vCA1 remain uncharacterized. The central hypothesis of this proposal is that vCA1 receives olfactory information along structured projections from pPIR and encodes information about odor identity in patterns of neuronal activity. In Aim 1, neuroanatomic studies will identify principles of spatial organization of feedforward projections from pPIR to vCA1. Viral-based tracing approaches will be used to elucidate the cell-types in pPIR that project to vCA1 and to determine the topographic organization of their axonal arborizations within vCA1. In Aim 2, neurophysiologic studies will determine the coding of olfactory stimuli in vCA1. Extracellular electrophysiology will be used to record vCA1 responses during presentation of olfactory stimuli, and the coding of odorant identity in single neurons and populations of neurons will be evaluated using statistical and computational approaches. This proposed study advances Theme 1 of the NIDCD’s 2023-2027 Strategic Plan to identify and characterize neural circuits involved in normal central olfactory processing. The short-term significance of this research is that it will provide fundamental basic science knowledge of the structure and function underlying healthy olfactory coding in a higher-level limbic brain region. The long-term objective is to enable future studies of central mechanisms underlying olfactory deficits in neurodegenerative diseases known to affect ventral hippocampus. This research training project will be carried out by the applicant in the Padmanabhan Laboratory at the University of Rochester. This environment is optimally suited to providing the applicant training in advanced computational approaches for neuroanatomic and neurophysiologic analyses and professional development in the field of chemosensory research. This training fellowship will prepare her to perform independent research on chemosensation within the field of neurology as a physician-scientist.
