The proposed research aims to elucidate the integrative mechanisms of olfactory bulb mitral cells, particularly as they relate to glomerular pattern analysis in the olfactory bulb. Two novel properties of mitral cells, membrane potential bistability and long lasting depolarizations (LLDs), are the specific focus of biophysical and pharmacological measurements to determine the underlying intrinsic currents and synaptic mechanisms producing these two properties of mitral cells. A novel slice preparation of early postnatal mouse brain which retains connections between olfactory neurons and olfactory bulb will be used to test specific hypotheses concerning the integrative functions of bistability and LLDs. Voltage clamp protocols will be used to characterize the activation and inactivation curves of intrinsic and synaptically activated currents in mitral cells elicited by antidromic stimulation of the lateral olfactory tract and orthodromic stimulation of the olfactory nerve. Dual intracellular recordings from the apical dendrite and soma of a mitral cell are proposed as are pairwise recordings from two mitral cells receiving input from the same glomerulus. Cross correlation techniques will be applied to test whether LLDs lead to synchronization of the mitral cell population with apical dendrites in the same glomerulus. Dual mitral cell recordings will also be used to test the hypothesis that bistability regulates the sensitivity of mitral cells to olfactory nerve inputs and functions as a temporal amplifier of lateral inhibition. The development of a viable olfactory bulb slice preparation from postnatal mouse makes possible the visualization of mitral cells with DIC/IR optics so that biophysical and integrative synaptic mechanisms can be made routinely with dual intracellular recordings. Normal and transgenic mice will be used to address questions of neurotransmitter receptor roles in mitral cell integrative mechanisms. Preliminary data show that the proposed techniques are working in the PI?s laboratory.
Showing the most recent 10 out of 30 publications
