Dynamics of Olfactory Processing: Segmentation in the Piriform Cortex

Abstract Dynamics of Olfactory Processing: Segmentation in the Piriform Cortex The proposed research aims to uncover fundamental principles of sensory processing by examining how the piriform cortex (PCx) in the mammalian brain encodes and represents olfactory information. This work is critical for advancing our understanding of neural coding, which has broad implications for sensory neuroscience and can inform approaches to neurological disorders that affect sensory perception and processing. Our study leverages innovative techniques to record from hundreds of PCx neurons in awake, head-fixed mice while using optogenetics to stimulate the olfactory bulb (OB) in precise, spatiotemporally defined patterns and manipulate neural circuits with novel tools to reveal underlying mechanisms. These methods will allow us to test our overarching hypothesis that the PCx segments incoming OB input into discrete temporal packets within a respiratory cycle. To this end, we propose the following aims: Aim 1: Determine the temporal selectivity of PCx responses to OB stimulation. We hypothesize that PCx neurons jointly encode both OB input and respiration phase. We will test this aim by delivering brief single light pulses to different dorsal OB spots, aligning stimulation with the respiration phase. We predict that PCx cells are tuned to respiration phase, showing varying amplitudes but invariant phase preferences across OB inputs. Aim 2: Investigate the neural circuit mechanisms underlying PCx respiration phase preferences. By performing various targeted circuit perturbations, we will test the following hypotheses: We hypothesize that phase tuning is reafferent, that feedback inhibition modulates response gain and sharpens tuning, and recurrent circuitry redistributes phase preferences to uniformly tile the sniff cycle. Aim 3: Assess whether PCx responses to odors are phase-locked. Ultimately, we need to test the hypothesis that PCx responses to odors are segmented and exhibit phase tuning. Therefore, we will (3.1) deliver multiple odors using 1-sec. odor puffs. Unlike the OB, we hypothesize that cells responding to multiple odors should show different amplitudes but identical latencies. Achieving these aims, our research will reveal, characterize, and mechanistically probe a novel framework for understanding how odor information is encoded in the PCx. This knowledge could eventually lead to novel strategies for diagnosing and treating sensory processing disorders and enhance our ability to develop artificial sensory systems.