The properties of voltage gated potassium channels and synaptic transmission of hippocampal inhibitory neurons in the developing brain was investigated. A major part of our effort is to understand the ionic mechanisms which regulate the activity of these cells and how these mechanisms impact hippocampal function using patch clamp, immunohistochemical and molecular techniques. Our work over the past year has focused on particular populations of inhibitory neurons of the CA1 and CA3 subfields. We have demonstrated the lack of a presynaptic form of cAMP-dependent long term potentiation at excitatory synapses onto st. lucidum interneurons. In addition we have shown that glutamate receptors on single st. lucidum interneurons comprise two main subtypes; Ca2+-permeable and Ca2+-impermeable. Analysis of the afferent innervation of these receptors demonstrates a specific innervation of Ca2+-permeable receptors by dentate granule cell mossy fibers. In contrast receptors innervated by CA3 pyramidal neuron collaterals are made exclusively onto Ca2+- impermeable receptors. In addition we have characterized the roles of several members of the Shaker family of potassium channels expressed on inhibitory neurons using both a combined electrophysiological and immunohistochemical approach. Specifically we have determined the roles of voltage-gated currents in st. oriens-alveus interneurons and their modulation by arachidonic acid. Analysis of the subcellular distribution of Kv2.1 has revealed a specific localization of channels at dendritic sites closely apposed to astrocytes and also a perisynaptic localization at inhibitory but not excitatory synapses. Furthermore progress has been made to determine how """"""""knock-out"""""""" of this K channel subunit by antisense oligonucleotides impacts the physiological function of the hippocampal formation.
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