Modeling Hippocampal CA1 Gabaergic Synapses of Audiogenic Rats

Author(s)

Pena, Rodrigo F. O. ^[1] ; Ceballos, Cesar Celis ^{[2, 1]} ; De Deus, Junia Lara ^[2] ; Roque, Antonio Carlos ^[1] ; Garcia-Cairasco, Norberto ^[2] ; Leao, Ricardo Mauricio ^[2] ; Siqueira Cunha, Alexandra Olimpio ^[2]

Affiliation

^[1] Univ Sao Paulo, Sch Philosophy Sci & Letters, Dept Phys, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: International Journal of Neural Systems; v. 30, n. 5 MAY 2020.
• Web of Science Citations: 0

Abstract

Wistar Audiogenic Rats (WARs) are genetically susceptible to sound-induced seizures that start in the brainstem and, in response to repetitive stimulation, spread to limbic areas, such as hippocampus. Analysis of the distribution of interevent intervals of GABAergic inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal cells showed a monoexponential trend in Wistar rats, suggestive of a homogeneous population of synapses, but a biexponential trend in WARs. Based on this, we hypothesize that there are two populations of GABAergic synaptic release sites in CA1 pyramidal neurons from WARs. To address this hypothesis, we used a well-established neuronal computational model of a CA1 pyramidal neuron previously developed to replicate physiological properties of these cells. Our simulations replicated the biexponential trend only when we decreased the release frequency of synaptic currents by a factor of six in at least 40% of distal synapses. Our results suggest that almost half of the CABAergic synapses of WARS have a drastically reduced spontaneous release frequency. The computational model was able to reproduce the temporal dynamics of GABAergic inhibition that could underlie susceptibility to the spread of seizures. (AU)

• FAPESP's process: 15/22327-7 - Analysis of electrophysiological and morphofunctional properties of neurons in the central nucleus of inferior colliculus related to genesis and spreading of sound-induced convulsive seizures
• Grantee: Alexandra Olimpio Siqueira Cunha
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/07699-0 - Research, Innovation and Dissemination Center for Neuromathematics - NeuroMat
• Grantee: Oswaldo Baffa Filho
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/50122-0 - Dynamic phenomena in complex networks: basics and applications
• Grantee: Elbert Einstein Nehrer Macau
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/01607-4 - High intensity sound stimulation and synaptic plasticity
• Grantee: Ricardo Mauricio Xavier Leão
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/25667-8 - Mechanisms of propagation of epileptiform activity in a large-scale cortical model
• Grantee: Rodrigo Felipe de Oliveira Pena
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)