Intrinsic and synaptic properties of hippocampal CA1 pyramidal neurons of the Wistar Audiogenic Rat (WAR) strain, a genetic model of epilepsy

Despite the many studies focusing on epilepsy, a lot of the basic mechanisms underlying seizure susceptibility are mainly unclear. Here, we studied cellular electrical excitability, as well as excitatory and inhibitory synaptic neurotransmission of CA1 pyramidal neurons from the dorsal hippocampus o...

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Published in:Scientific reports 2018-07, Vol.8 (1), p.10412-11, Article 10412
Main Authors: Cunha, Alexandra Olimpio Siqueira, Ceballos, Cesar Celis, de Deus, Júnia Lara, Pena, Rodrigo Felipe de Oliveira, de Oliveira, José Antonio Cortes, Roque, Antonio Carlos, Garcia-Cairasco, Norberto, Leão, Ricardo Maurício
Format: Article
Language:English
Subjects:
Brain slice preparation
Epilepsy
Excitability
Excitatory postsynaptic potentials
Glutamic acid receptors (ionotropic)
Hippocampus
Inhibitory postsynaptic potentials
Kindling
N-Methyl-D-aspartic acid receptors
Neurotransmission
Pyramidal cells
Seizures
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Summary:Despite the many studies focusing on epilepsy, a lot of the basic mechanisms underlying seizure susceptibility are mainly unclear. Here, we studied cellular electrical excitability, as well as excitatory and inhibitory synaptic neurotransmission of CA1 pyramidal neurons from the dorsal hippocampus of a genetic model of epilepsy, the Wistar Audiogenic Rat (WARs) in which limbic seizures appear after repeated audiogenic stimulation. We examined intrinsic properties of neurons, as well as EPSCs evoked by Schaffer-collateral stimulation in slices from WARs and Wistar parental strain. We also analyzed spontaneous IPSCs and quantal miniature inhibitory events. Our data show that even in the absence of previous seizures, GABAergic neurotransmission is reduced in the dorsal hippocampus of WARs. We observed a decrease in the frequency of IPSCs and mIPSCs. Moreover, mIPSCs of WARs had faster rise times, indicating that they probably arise from more proximal synapses. Finally, intrinsic membrane properties, firing and excitatory neurotransmission mediated by both NMDA and non-NMDA receptors are similar to the parental strain. Since GABAergic inhibition towards CA1 pyramidal neurons is reduced in WARs, the inhibitory network could be ineffective to prevent the seizure-dependent spread of hyperexcitation. These functional changes could make these animals more susceptible to the limbic seizures observed during the audiogenic kindling.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-28725-y