The aim of this project is to characterize the properties of voltage gated channels and synaptic transmission of hippocampal inhibitory neurons in the developing brain and how these properties impact hippocampal function under both physiological and pathological conditions. Although much is known about their neurochemistry, their role in the local circuits and the basic electrophysiological properties of inhibitory interneurons, little is known about the specific ionic or ligand gated channels expressed on this highly divergent population of cells. 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 focussed on particular populations of inhibitory neurons of the CA1 stratum oriens/alveus and pyramidal cell layers. Particularly we have characterized the complement of potassium channels present on these cells using both a combined electrophysiological and immunohistochemical approach. We have determined the roles of voltage-gated currents in st. oriens-alveus interneurons in determining the action potential and firing patterns of these cells. In addition we have investigated the developmental expression and functional role of the K channel 2subunit Kv3.1 in parvalbumin containing interneurons of st. pyramidale.The role of various types of interneuron during the plastic phenomena of long term depression and potentiation using perforated patch and paired reording techniques has also been studied.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
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State
Country
United States
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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
Plant, Karen; Pelkey, Kenneth A; Bortolotto, Zuner A et al. (2006) Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation. Nat Neurosci 9:602-4
Torborg, Christine L; Berg, Allison P; Jeffries, Brian W et al. (2006) TASK-like conductances are present within hippocampal CA1 stratum oriens interneuron subpopulations. J Neurosci 26:7362-7
McBain, Chris J; Traynelis, Stephen F (2006) Malevolent lurkers no more: NMDA receptors come of age. J Physiol 575:317-8
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

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