The recruitment and function of inhibitory interneurons in olfactory bulb processing

Inhibitory interneurons are the “shush”-ers of the brain—their output causes a reduction in the output of other neurons. Inhibitory interactions play a critical role in the olfactory bulb, where they shape olfactory representations that guide behavior. However, the mechanisms by which interneuron activation improves olfactory function remain debated. In particular, the relative importance neural activity over short periods of time (~tens of milliseconds) versus long periods of time (hundreds to thousands of milliseconds) has provoked significant debate. Granule cells are inhibitory interneurons in the olfactory bulb that can respond and influence olfactory bulb activity across a wide range of timescales. The first part of this dissertation investigates the physiological mechanisms driving the timing of granule cell recruitment. We found that the specific timing of recruitment depends on the timing of synaptic excitation delivered from tufted cells. Tufted cells (unlike the more commonly studied mitral cells) are able to fire at long latencies due to intrinsic membrane properties that allow them to integrate weak inputs slowly while responding rapidly to strong inputs. Computational modeling revealed that the long-latency inhibition generated by this mechanism can improve performance on stimulus discrimination tasks. The second portion of this dissertation focuses on the downstream effects of granule cell recruitment. Highly correlated spiking can be advantageous for propagating information. However, these same correlations limit encoding by introducing redundancy. We investigated how granule cell recruitment altered correlations between mitral cell pairs across timescales. We found that granule cell recruitment increased fast timescale correlations (i.e. synchronous spiking) while simultaneously decreasing slow timescale correlations (i.e. firing rate similarity). Using computational modeling, we show that timescale-dependent correlation changes are functionally advantageous because they can circumvent the tradeoff between propagation and encoding. Taken together, these studies extend our understanding of olfactory bulb physiology by providing a mechanistic description of how inhibitory circuits shape activity across timescales. Our results indicate that granule cell recruitment requires dynamic and stimulus-dependent interactions between mitral, tufted, and granule cells, and that the inhibition recruited by this mechanism works at multiple timescales to effectively encode and propagate stimulus information