Investigating Cortical Readout of Temporal Codes for Olfaction

Abstract

In all sensory systems, arrays of receptors respond to stimuli over both space and time. Whether and how the precise temporal pattern of receptor activation impacts the activity of downstream brain regions remains unclear. This is the case in the olfactory system, where odors activate stereotyped spatiotemporal sequences of olfactory bulb (OB) glomeruli, whose responses reflect the activity of olfactory receptor neurons. These glomeruli project to downstream piriform cortex (PCx), where ensembles of activated neurons represent the odor percept. Each odor stimulus activates a specific subset of glomeruli in a specific temporal order, leading to the hypothesis that both the identity and timing of glomerular responses convey odor information. However, the extent to which each of these response features influences cortical activity is not known.To address this question, I used patterned optogenetic stimulation to precisely and independently control the spatial and temporal dynamics of the glomeruli. I simultaneously measured cortical responses to glomerular stimulation using large-scale electrophysiological recordings of populations of PCx neurons in awake, head-fixed mice. My experiments revealed that PCx reads out the temporal pattern of “odor-like” optogenetic input sequences with millisecond precision. Using reduced stimuli to probe the computations underlying this phenomenon, I demonstrated that in addition to the identity of activated glomeruli, cortical neurons are tuned to the phase of glomerular stimulation relative to the respiration cycle. Additional circuit and experimental manipulations revealed that this tuning is gated by oscillations imposed by respiratory drive to the PCx network, and is further shaped by cortical recurrent circuits. Thus, my experiments reveal a central role for spike timing in transmitting information from the OB to PCx. Moreover, my findings provide novel insights into the computational principles and circuit mechanisms governing the readout of neural population codes.