Project Summary The main goal of the studies within this application is to define the role that a specific class of GABAergic neurons, called periglomerular (PG) cells, has in mediating information transfer in the olfactory bulb. The main hypothesis to be tested is that PG cells, through a feed-forward inhibitory mechanism onto output mitral cells, function to gate signals of different strengths, favoring strong signals over weak signals. Such a mechanism may be functionally important for enhancing differences between closely related odors. Each aim of this application will test a specific hypothesis that follows from this mechanism. The first aim will examine the general response profile of mitral cells, testing the specific hypothesis that "modules" of mitral cells engage in all-or-none responses to sensory input that occur simultaneously throughout the modular network. The second aim will then test the hypothesis that PG cells gate the generation of these mitral cell network responses. Experiments in aims 1 and 2 will primarily be done using electrophysiological techniques combined with pharmacological manipulations in rat in vitro olfactory bulb slices. The 3rd aim will test exactly how PG cells modulate mitral cell network responses, testing the specific hypothesis that PG cells inhibit mitral cells through a feed-forward mechanism. This hypothesis will be tested using calcium imaging of PG cells and electrophysiological recording of mitral cells in rat olfactory bulb slices. Taken together, the studies within this application will establish a role for PG cells in regulating information transfer through the first central relay of the olfactory system, the olfactory bulb. Relevance The studies described within this application will define mechanisms that inhibitory interneurons use to influence the excitability of neuronal circuits. Throughout the brain, dysfunction of this type of inhibition can lead to human disorders, perhaps the most notable being epilepsy. These studies will thus provide information that will aide in the understanding and treatment of neurological disorders, in addition to basic information about sensory processing.