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The Journal of Neuroscience, June 17, 2009, 29(24):7846-7856; doi:10.1523/JNEUROSCI.6199-08.2009

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Cellular/Molecular
Dysfunction of the Dentate Basket Cell Circuit in a Rat Model of Temporal Lobe Epilepsy

Wei Zhang¹ and Paul S. Buckmaster^1,2

¹Departments of Comparative Medicine and ²Neurology and Neurological Sciences, Stanford University, Stanford, California 94305-5342

Correspondence should be addressed to Paul S. Buckmaster, Department of Comparative Medicine, 300 Pasteur Drive, R321 Edwards Building, Stanford University, Stanford, CA 94305-5342. Email: psb{at}stanford.edu

Temporal lobe epilepsy is common and difficult to treat. Reduced inhibition of dentate granule cells may contribute. Basket cells are important inhibitors of granule cells. Excitatory synaptic input to basket cells and unitary IPSCs (uIPSCs) from basket cells to granule cells were evaluated in hippocampal slices from a rat model of temporal lobe epilepsy. Basket cells were identified by electrophysiological and morphological criteria. Excitatory synaptic drive to basket cells, measured by mean charge transfer and frequency of miniature EPSCs, was significantly reduced after pilocarpine-induced status epilepticus and remained low in epileptic rats, despite mossy fiber sprouting. Paired recordings revealed higher failure rates and a trend toward lower amplitude uIPSCs at basket cell-to-granule cell synapses in epileptic rats. Higher failure rates were not attributable to excessive presynaptic inhibition of GABA release by activation of muscarinic acetylcholine or GABA_B receptors. High-frequency trains of action potentials in basket cells generated uIPSCs in granule cells to evaluate readily releasable pool (RRP) size and resupply rate of recycling vesicles. Recycling rate was similar in control and epileptic rats. However, quantal size at basket cell-to-granule cell synapses was larger and RRP size smaller in epileptic rats. Therefore, in epileptic animals, basket cells receive less excitatory synaptic drive, their pools of readily releasable vesicles are smaller, and transmission failure at basket cell-to-granule cell synapses is increased. These findings suggest dysfunction of the dentate basket cell circuit could contribute to hyperexcitability and seizures.

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Received Dec. 31, 2008; revised April 22, 2009; accepted May 12, 2009.

Correspondence should be addressed to Paul S. Buckmaster, Department of Comparative Medicine, 300 Pasteur Drive, R321 Edwards Building, Stanford University, Stanford, CA 94305-5342. Email: psb{at}stanford.edu

This article has been cited by other articles:

				W. Zhang, R. Yamawaki, X. Wen, J. Uhl, J. Diaz, D. A. Prince, and P. S. Buckmaster Surviving Hilar Somatostatin Interneurons Enlarge, Sprout Axons, and Form New Synapses with Granule Cells in a Mouse Model of Temporal Lobe Epilepsy J. Neurosci., November 11, 2009; 29(45): 14247 - 14256. [Abstract] [Full Text] [PDF]

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