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

Autor(es)

Siqueira Cunha, Alexandra Olimpio ^[1] ; Ceballos, Cesar Celis ^{[1, 2]} ; de Deus, Junia Lara ^[1] ; de Oliveira Pena, Rodrigo Felipe ^[2] ; Cortes de Oliveira, Jose Antonio ^[1] ; Roque, Antonio Carlos ^[2] ; Garcia-Cairasco, Norberto ^[1] ; Leao, Ricardo Mauricio ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Philosophy Sci & Letters Ribeirao Preto, Dept Phys, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 8, JUL 10 2018.
• Citações Web of Science: 2

Resumo

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. (AU)

• Processo FAPESP: 15/50122-0 - Fenômenos dinâmicos em redes complexas: fundamentos e aplicações
• Beneficiário: Elbert Einstein Nehrer Macau
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/01607-4 - Estimulação auditiva de alta intensidade e plasticidade sináptica
• Beneficiário: Ricardo Mauricio Xavier Leão
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/50261-4 - Neurociências, epilepsia e arte: caracterização interdisciplinar da cepa WAR e modelos de epilepsia correlacionados: as oficinas Da Vinci, divulgação científica e quebras de estigmas em epilepsia
• Beneficiário: Norberto Garcia Cairasco
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/22327-7 - Estudo das propriedades eletrofisiológicas e morfofuncionais de neurônios do núcleo central do colículo inferior envolvidas com a gênese e propagação das crises audiogênicas
• Beneficiário: Alexandra Olimpio Siqueira Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 13/07699-0 - Centro de Pesquisa, Inovação e Difusão em Neuromatemática - NeuroMat
• Beneficiário: Oswaldo Baffa Filho
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs