Circuit functions of fast-spiking interneurons in the main olfactory bulb

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PROJECT SUMMARY/ABSTRACT The olfactory system is critical to several aspects of behavior and survival in mammals, including humans. The olfactory bulb is the first processing station of the olfactory system and constitutes an exceptional model system for the study of neural coding, capable of encoding a highly complex sensory space within a compact and well- organized structure. Understanding local circuit computation within the olfactory bulb will thus provide key insight into fundamental principles of brain function. Broad perturbation of synaptic inhibition within the olfactory bulb significantly disrupts projection mitral/tufted cell synchronization and olfactory-guided behavior, underscoring a central role of inhibitory interneurons in local circuit computation. In contrast to other regions of the brain such as neocortex and hippocampus, however, fundamental understanding of how the diverse inhibitory interneurons within the olfactory bulb specifically support neural coding has remained elusive, with detailed knowledge of how unitary synaptic interactions contribute to the precise regulation of mitral/tufted cell spike timing in particular lacking. To advance understanding of local circuit computation and neural coding in the olfactory bulb, this project will therefore directly examine unitary synaptic interactions between mitral/tufted cells and a highly-conserved but understudied class of fast-spiking interneurons, using whole-cell pair recordings in acute mouse brain slices together with pharmacology, morphological reconstruction, immunostaining, and simulations. Investigation will specifically address three aims: 1) determine how fast-spiking interneurons regulate mitral/tufted cell spike timing, 2) determine how dendritic computation supports fast-spiking interneuron function, and 3) determine how fast-spiking interneuron signaling adapts with neural activity.