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Dysfunction of the dentate basket cell circuit in a rat model of temporal lobe epilepsy.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2009 Jun 17; Vol. 29 (24), pp. 7846-56. - Publication Year :
- 2009
-
Abstract
- 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.
- Subjects :
- Analysis of Variance
Animals
Atropine Derivatives pharmacology
Disease Models, Animal
Electric Stimulation methods
Epilepsy, Temporal Lobe chemically induced
Epilepsy, Temporal Lobe metabolism
Epilepsy, Temporal Lobe physiopathology
GABA Antagonists pharmacology
In Vitro Techniques
Lysine analogs & derivatives
Lysine metabolism
Male
Muscarinic Agonists pharmacology
Muscarinic Antagonists pharmacology
Neurons classification
Neurons drug effects
Neurons metabolism
Patch-Clamp Techniques methods
Phosphinic Acids pharmacology
Pilocarpine pharmacology
Propanolamines pharmacology
Rats
Rats, Sprague-Dawley
Synaptic Potentials drug effects
Synaptophysin metabolism
Time Factors
Dentate Gyrus pathology
Epilepsy, Temporal Lobe pathology
Nerve Net physiopathology
Neurons physiology
Synaptic Potentials physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 29
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 19535596
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.6199-08.2009