The olfactory bulb performs a critical role in encoding olfactory information and routing it to downstream brain regions. This proposal defines an experimental plan to determine the subtypes of local interneurons that provide inhibitory input to mitral cells, one of the main classes of output cells in the olfactory bulb. These inhibitory circuts govern how the circuit is activated and sculpt mitral cell activity. I will first determine the speific subtypes of local interneurons that have axon terminals in layers containing mitral cell processes. There are several relatively unexplored interneuron subtypes in the olfactory bulb that could synapse onto mitral cells, in addition to commonly studied granule cells. My preliminary studies have suggested that one of these, oriented horizontal cells, monosynaptically inhibits mitral cells. Using whole-cell patch clamp electrophysiology and live 2-photon imaging in acute rodent brain slices, I will define the morphological and electrophysiological properties of interneurons with axonal ramifications near the mitral cell layer. Using visualized paired recordings, I will then determine which of these interneuron subtypes actually inhibits mitral cells and define the functional consequences of this inhibition. Next, I will trigger excitation onto these local interneurons by stimulating olfactory sensory neuron axons and determine whether horizontal (and related) classes of interneurons are activated by relatively few glomerular columns (like mitral and tufted cells are) or, instead, integrate synaptic input widely from multiple input glomeruli. Finally, I will also use an in vitro combined olfactory bulb/piriform cortex slice preparation to determine if these interneurons receive centrifugal input from olfactory cortex. Using these strategies, I will determine the set o olfactory bulb circuits that inhibit mitral cells and how this inhibition affects mitral cell functon.
This study seeks to elucidate how the olfactory bulb processes smell information as it is routed from the nasal epithelium to where it is decoded in higher brain regions. During the course of this research, I will define how a local circuit within the olfactory bulb targets one group of olfactory bulb output neurons and differentiates their activity. This is not only important for understanding olfactory processing and the pathology of olfactory defects, understanding this circuit will enhance our understanding of fundamental processes in neuroscience- as circuits like these in the olfactory bulb are repeated as modules throughout the central nervous system. Understanding the mechanisms governing local inhibition here will not only help us understand how smell information is processed in the olfactory bulb, but will also understand how information is processed using similar arrangements of circuits in other regions throughout the brain.