NEURONAL NETWORKS AND DYNAMICS INVOLVED IN MOUSE AUDIOGENIC SEIZURES

Aims: Epilepsy is a frequent neurological disease, affecting ~1% of the population. Mouse audiogenic seizures (AS) are a model of reflex seizures triggered by exposure to an intense sound (> 100 dB). The inferior colliculus (IC), a major brainstem auditory nucleus, has been previously shown to be necessary for AS. One major unsolved question in epilepsy pathophysiology concerns the respective roles of subcortical and cortical structures in seizure generation. Epilepsy is generally considered a cortical disease, but the contribution of subcortical structures may be underestimated due to recording limitations. Our aim is to investigate the respective roles of subcortical (IC) and cortical (auditory cortex, AC) structures, sequentially involved in auditory processing, in the AS model. Methods: We use 2-photon (2P) calcium imaging to compare the dynamics of neuronal activation during AS in IC and AC at the single-cell level, and optogenetics to
study the impact of activity modulation on AS. Results: IC 2P calcium imaging shows a wave of massive neuronal activation at the initial stage of the seizure (wild running, WR), with epilepsy-like spatial and temporal dynamics; while AC shows a mostly suppressed activity. IC optogenetic activation recapitulates a complete seizure (WR followed by convulsions), while AC bilateral optogenetic activation triggers only initial stages (WR). Conclusions: The IC, a subcortical auditory structure, is necessary and sufficient to trigger AS. IC display massive neuronal activation at the initial stage of AS. We show for the first time a spatio-temporal neuronal activation pattern evocative of epileptic dynamics within a subcortical structure.