Single-pulse electrical stimulation methodology in freely moving rat

•New methodology using single pulse electrical stimulation in freely moving rats.•Responses to electrical stimulation were recorded in cortex and striatum.•Significant differences between cortical and subcortical responses.•Later components in striatal responses compared to cortical ones. Cortico-cortical evoked potentials (CCEP) are becoming popular to infer brain connectivity and cortical excitability in implanted refractory epilepsy patients. Our goal was to transfer this methodology to the freely moving rodent. CCEP were recorded on freely moving Sprague-Dawley rats, from cortical and subcortical areas using depth electrodes. Electrical stimulation was applied using 1 ms biphasic current pulse, cathodic first, at a frequency of 0.5 Hz, with intensities ranging from 0.2 to 0.8 mA. Data were then processed in a similar fashion to human clinical studies, which included epoch selection, artefact correction and smart averaging. For a large range of tested intensities, we recorded CCEPs with very good signal to noise ratio and reproducibility between animals, without any behavioral modification. The CCEP were composed of different components according to recorded and stimulated sites, similarly to human recordings. We minimally adapted a clinically-motivated methodology to a freely moving rodent model to achieve high translational relevance of future preclinical studies. Our results indicate that the CCEP methodology can be applied to freely moving rodents and transferred to preclinical research. This will be of interest to address various neuroscientific questions, in physiological and pathological conditions.