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.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Intramural Research (Z01)
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Special Emphasis Panel (LCMN)
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Ho, T M; Pelkey, K A; Pelletier, J G et al. (2009) Burst firing induces postsynaptic LTD at developing mossy fibre-CA3 pyramid synapses. J Physiol 587:4441-54
Pelkey, Kenneth A; McBain, Chris J (2007) Differential regulation at functionally divergent release sites along a common axon. Curr Opin Neurobiol 17:366-73
Isaac, John T R; Ashby, Michael; McBain, Chris J (2007) The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity. Neuron 54:859-71
Ho, Michelle T-W; Pelkey, Kenneth A; Topolnik, Lisa et al. (2007) Developmental expression of Ca2+-permeable AMPA receptors underlies depolarization-induced long-term depression at mossy fiber CA3 pyramid synapses. J Neurosci 27:11651-62
Pelkey, Kenneth A; Yuan, Xiaoqing; Lavezzari, Gabriela et al. (2007) mGluR7 undergoes rapid internalization in response to activation by the allosteric agonist AMN082. Neuropharmacology 52:108-17
Lawrence, J Josh; Saraga, Fernanda; Churchill, Joseph F et al. (2006) Somatodendritic Kv7/KCNQ/M channels control interspike interval in hippocampal interneurons. J Neurosci 26:12325-38
Pelkey, Kenneth A; Topolnik, Lisa; Lacaille, Jean-Claude et al. (2006) Compartmentalized Ca(2+) channel regulation at divergent mossy-fiber release sites underlies target cell-dependent plasticity. Neuron 52:497-510
Banke, Tue G; McBain, Chris J (2006) GABAergic input onto CA3 hippocampal interneurons remains shunting throughout development. J Neurosci 26:11720-5
Lawrence, J Josh; Grinspan, Zachary M; Statland, Jeffrey M et al. (2006) Muscarinic receptor activation tunes mouse stratum oriens interneurones to amplify spike reliability. J Physiol 571:555-62
Lawrence, J Josh; Statland, Jeffrey M; Grinspan, Zachary M et al. (2006) Cell type-specific dependence of muscarinic signalling in mouse hippocampal stratum oriens interneurones. J Physiol 570:595-610

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