The overall goal of this proposal is to understand the functional mechanisms of inhibitory interneurons in the mammalian olfactory bulb. These interneurons, called granule cells and periglomerular (PG) cells, are often proposed to impact olfactory information processing in one of two ways, either by synchronizing the activity of the bulb's output neurons (mitral cells) or by mediating lateral inhibitory interactions between mitral cells. However, the functional mechanisms of the interneurons are not well-understood. Studies in the first two Specific Aims of this proposal use patch-clamp recordings from interneurons in olfactory bulb slices in order to evaluate two mechanistic aspects of interneurons that we predict are critical for function. These include the mechanisms of synaptic activation of interneurons by mitral cells (Aim 1) and mechanisms that couple the activity of different interneurons (Aim 2).
In Specific Aim 3, recordings from pairs of mitral cells in slices will be made to test the functional role of interneurons in synchronizing action potential-firing in mitral cells. A key novel aspect of our studies is our electrical stimulation paradigm. While previous studies have examined interneuron mechanisms under static conditions, we examine their functional properties under dynamic, more physiological conditions produced by low frequency stimulation of afferent olfactory nerve (ON) fibers. The results of our studies will lead to a direct understanding of how synchronized activity is generated in the bulb, and also point toward possible mechanisms that could alter such activity following olfactory learning or during pathological conditions, such as Alzheimer's and Parkinson's disease. In addition, our mechanistic studies of synchronized activity could provide insight into mechanisms of epileptogenic dysfunction in other brain circuits.
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