Olfactory bulb network computations underlie concentration invariant odor identification

Odors evoke distinct patterns of neural activity across different concentrations, both at the input level of olfactory sensory neurons (OSN) and glomeruli, as well as the next level, mitral/tufted cells (MTCs). What features of these patterns carry invariant information about odor identity and what are the neural mechanisms defining these features? To address this question, we designed an all-optical system to monitor the activity of many glomeruli and MT cells with high temporal resolution and developed an optogenetic method for establishing functional connectivity between glomeruli and MTCs. We combined two photon Ca2+ imaging with one photon patterned optogenetics in mice expressing a fast calcium indicator (GCaMP6f) in glomeruli and MTCs, and a light-sensitive opsin (ChR2) in OSNs. We found that the earliest activity of glomeruli and MTCs most reliably represented odor identity across concentrations. We found that MTCs connected to early activated glomeruli exhibited stereotypic excitatory responses following their parent glomeruli. At the same time, the odor responses of MTCs connected to later activated glomeruli were strongly affected by the inhibitory network evoked by earlier activated glomeruli. We probed the responsiveness of MTCs to glomerular activation using short optogenetic pulses in the presence of odor stimuli and found that MTCs can effectively transmit glomerular signals to the cortex only in a short temporal window at the beginning of the sniff cycle. Beyond this window, MTC responses were strongly suppressed by inhibition evoked by the presented odor. These findings reveal potential mechanisms for concentration invariant odor coding, and support the primacy model for olfactory information processing, wherein the earlier-activated glomeruli carry odor identity information.