Inhibition plays a central role in the nervous system, but many of its features remain mysterious. For example, there are many types of inhibitory neurons, each with strikingly-different shapes, electrical properties, and connections. However, when examined in other ways for example in terms of their activity to natural stimuli in the intact circuit in many cases these diverse types appear surprisingly uniform. While one suspects there must be a reason that the brain contains so many types of inhibitory neurons, currently the major tasks attributed to inhibition could seemingly be accomplished with far fewer types. The olfactory system has long been one of the most attractive systems for studying the roles of inhibition, in part because it spotlights many of its puzzles. Because olfaction has many different "processing streams" (a multitude of receptor genes to detect a multitude of chemicals), the olfactory system represents an excellent opportunity to look for specificity in the patterns of inhibitory function. However, using conventional techniques, the sheer diversity of olfactory systems also makes this a daunting challenge. Within the olfactory system, we will focus on a particular stage of processing called the glomerular layer, which collectively encodes all the information the animal has available about olfactory stimuli. We will leverage a new imaging technology developed in our laboratory, Objective-Coupled Planar Illumination (OCPI) microscopy, to image the glomerular layer of the accessory olfactory bulb in its entirety. This wil allow us to exhaustively analyze the interactions between different glomeruli. Our experiments will study the consequences of inhibition at two stages within the glomerular layer roughly, its inputs and outputs and thereby serve to test several candidate mechanisms of inhibitory specificity. Collectively, these experiments will reveal the "logic" of a key stage of sensory processing in the nervous system.
Diseases of the nervous system, such as epilepsy, involve a failure to inhibit inappropriate muscle movements and brain activity. Consequently, the pattern of inhibition is critical to normal brain function. The olfactory system is an excellent model for studying inhibition;this application proposes studies to unravel the specificity of inhibition durng natural function.
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