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. It is hoped that these mechanisms may be potentially exploited in the future treatment of a variety of pathological conditions such as electrographic seizure activity, ischemic cell damage and stroke. Our work over the past year has focused on a particular population of inhibitory neurons, the CA1 stratum oriens/alveus interneuron. Particularly we have begun to investigate and characterize the compliment of potassium (K) channels present on these cells using both an electrophysiological and a molecular approach. In addition we have begun to characterize the role of these stratum oriens/alveus interneurons during the plastic phenomena of long term depression and potentiation. The role of stratum oriens/alveus interneurons in the high K+ -induced electrographic seizure model of epilepsy has also been studied. The characterization of the basic physiological and pharmacological properties of these cells is an essential first step for the more detailed study proposed.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
City
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
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
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

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