The research project is directed towards studying the physiological and pathological properties of neurotransmitter-gated ion channels and voltage-gated channels on identified inhibitory interneurons of the hippocampus. The high potassium model of hypersynchronous, epileptiform activity was used to study the cellular elements responsible for seizure initiation and maintenance in the hippocampus. Patch clamp electrophysiology was used to record from inhibitory interneurons located within the hippocampus slice preparation. Elevation of the potassium ion concentration bathing the hippocampal slice resulted in a direct excitation of all inhibitory neurons. These cells were entrained by the ongoing synaptic activity and participated in the burst-firing discharge of the neuronal population. Antagonists of the metabotropic glutamate receptor reversibly abolished the burst firing observed in these neurons, an effect mimicked by antagonists of haem oxygenase. Blockade of these receptors was without effect on the ongoing inhibitory and excitatory synaptic currents received by the interneuron population. This data suggests that the involvement of inhibitory interneurons in seizure episodes are dependent on the activation of the metabotropic glutamate receptor population.

Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
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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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