Neural circuits supporting olfactory computation and perception

About This Grant

PROJECT SUMMARY This project aims to uncover the circuit and computational mechanisms that support olfactory perception. Odors evoke spatially distributed patterns of activity across olfactory bulb (OB) glomeruli, which in turn drive temporally structured responses in mitral and tufted cells (MTCs), the OB’s output neurons. These responses are shaped by local inhibitory circuits before reaching higher-order regions such as the piriform cortex (PCx). However, how spatiotemporal OB activity is organized, transformed by local interactions, and decoded by the PCx remains unclear. I will combine two-photon calcium imaging with fast GCaMP8 indicators, patterned optogenetics, and large-scale silicon probe recordings to study these dynamics in awake mice. Aim 1 (K99 phase) will determine how glomerular input and MTC output sequences are structured during odor responses. I will test whether the temporal order of glomerular activation predicts MTC excitability, shaped by lateral inhibition. I will map functional glomerulus to MTC connectivity and relate temporal features to odor tuning. Aim 2 (K99) will probe how recurrent MTC interactions shape odor representations. Using a novel all- optical method combining 2P stimulation and imaging, I will characterize how MTCs influence each other based on tuning similarity. I hypothesize that recurrent motifs enhance similarity among similarly tuned MTCs and decorrelate dissimilar ones. In Aim 3 (R00) I will extend this survey to the cortex and determine how OB output is integrated by PCx and modulated by experience. I hypothesize that MTCs with similar odor tuning and timing preferentially converge onto shared PCx targets, and that this convergence is shaped by Hebbian-like learning. I will test this with two-photon imaging of glomerular odor tuning, optogenetic stimulation of targeted glomeruli and large-scale PCx recordings and examine how repeated odor experience modifies the structure of OB to PCx functional connectivity. This work will define how spatiotemporal odor codes are transformed from OB to PCx and how experience refines this transformation. The K99 phase will develop circuit mapping and all-optical methods (Aims 1–2); the R00 phase will expand my focus to PCx decoding and plasticity (Aim 3). These studies will provide fundamental mechanistic insight into sensory computation and provide me training in advanced techniques for recording and manipulating neural activity, as well as computational expertise. These research goals will be achieved by direct guidance from my mentors, Dr. Dmitry Rinberg and Dr. Gyorgy Buzsaki, my postdoctoral committee, as well as the collaborative environment at NYU. My training plan provides a detailed strategy to acquire technical, computational, and conceptual skills that are crucial for these proposed experiments. Importantly, these skills will also serve as the foundation of my independent laboratory, focusing on the transformation from sensory processing to behavior.