Standardization of the video-electroencephalography experimental protocol of the substantia nigra pars compacta activity, following limbic recruitment induced by chronic seizures in the Wistar Audiogenic Rat strain

• Grant number: 23/02546-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Norberto Garcia Cairasco
• Grantee: Mariana Grigório de Sant'Ana
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Epilepsy is a serious illness consisting of seizures resulting from hypersynchronism and hyperexcitability in the brain. In certain epilepsies, the involvement of limbic structures such as the hippocampus stands out, especially susceptible to seizures. On the other hand, studies indicate that the substantia nigra pars compacta (SNpc) is a structure possibly involved in the suppression of epileptic seizures, which can occur, also due to the interactions of neural networks with the hippocampus and by the presence of dopaminergic (DA) neurons. Among the so-called audiogenic strains, genetically-selected to present the epileptic phenotype when exposed to sound stimuli, the Wistar Audiogenic Rat (WAR) presents changes that make them more susceptible to epileptic seizures and different, especially neuropsychiatric comorbidities. Even though, chronic seizures, or audiogenic kindling (KA) are an effective way to promote the recruitment of limbic structures during seizures (i.e., the expansion of the circuits involved in the seizures), some animals are resistant to such recruitment. Then our objective is to evaluate the influence of SNpc in blocking limbic seizures during the KA protocol in WAR. For this, 16 WAR animals will be submitted to KA with 2 stimuli per day for 10 days (total 20 stimuli) and then, based on their response to KA, divided into animals with and without limbic recruitment. Subsequently, the stereotaxic surgery procedure will be performed for the implantation of electrodes in the hippocampus and SNpc and then an acute acoustic stimulus will be performed simultaneously with video recording and electroencephalogram (EEG). Finally, the animals will be submitted to the perfusion and tissues will be collected. Our hypothesis is that the SNpc EEG activity will be associated to the behavioral and EEGgraphic modifications resulting from the progression of the KA and will be different depending on whether or not the animals recruit limbic regions, assessed by video and EEG of the hippocampus.