Investigating cortical readout of temporal codes for olfaction

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ABSTRACT In the brain, stereotyped sequences of neural activity have been shown to correlate with a diverse array of behaviors and cognitive processes. While neural sequences have been characterized extensively from an encoding perspective, the effects of sequence activity on downstream reader networks remain relatively unexplored. A key example is in the olfactory system, where odors activate stereotyped spatiotemporal sequences of olfactory bulb glomeruli. The temporal structure of glomerular activity is thought to convey information about odor quality to the rest of the brain. However, the sensitivity of populations of neurons in downstream piriform cortex (PCx) to the precise timing of glomerular sequences is not known. Recent advances in light patterning technologies have made it possible to optogenetically activate sequences of glomeruli with high temporal precision, providing a means to investigate the independent impact of sequence timing on neural activity in PCx. In my early graduate work, I built and validated a system to perform patterned optogenetic stimulation of olfactory bulb glomeruli in awake mice. I established methods to use this system in tandem with multichannel electrode recordings of large populations of neurons in PCx. In preliminary experiments, I have observed that population activity in PCx is highly dependent on the precise timing of glomerular responses. In this proposal, I will test the central hypothesis that intra-cortical recurrent circuits enforce the precise readout of sequential inputs to PCx. In my first aim, I will determine how individual PCx cells integrate temporally distributed inputs. Then, in aims 2 and 3, I will use cell-type specific optogenetics to delineate the respective contributions of intra-cortical inhibition and recurrent excitation within PCx to these temporally specific responses. The results of these experiments will provide a quantitative and mechanistic understanding of how neural sequence readout is coordinated in cortical circuits.