Sequence decoding with millisecond precision in the early olfactory system

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. In the olfactory system, odors activate stereotyped spatiotemporal sequences of olfactory bulb (OB) glomeruli, whose responses reflect the activity of olfactory receptor neurons. These glomeruli project via OB mitral and tufted (M/T) cells to downstream piriform cortex (PCx), forming a shallow circuit through which to assess how temporal patterns of receptor activity are encoded at each stage of processing from the periphery to cortex.

Using targeted patterned optogenetic stimulation of glomeruli in awake, head-fixed mice while recording from large populations of PCx neurons, we have revealed that neural population responses in PCx are exquisitely sensitive to the specific timing with which glomeruli are sequentially stimulated throughout a single sniff cycle (~150ms). We hypothesized that this temporal selectivity is conferred by cortical inhibitory circuits. We therefore stimulated sequences of glomeruli while optogenetically suppressing PCx inhibitory interneurons. Suppressing cortical inhibition substantially increased the magnitude of PCx responses but, surprisingly, had little effect on temporal selectivity. Instead, we found that OB M/T cells also exhibit temporally selective responses, suggesting that sequence selectivity is computed by OB circuits and then relayed to downstream cortical networks. Together, our findings provide novel insights into the computational principles and mechanisms that govern neural sequence readout in cortical circuits.