Abstracts

Rationale: Epilepsies share common high-level alterations, such as cognitive deficits, anxiety, and depression, despite a large variety of underlying structural modifications. This raises the possibility of fundamental alterations in the way information conveyed by neural firing is maintained and dispatched in epileptogenic networks. Using the rat pilocarpine experimental model of epilepsy we tested the hypothesis of altered information processing, analyzing how neurons in the hippocampus and the entorhinal cortex store and exchange information during slow and theta oscillations. State-based information processing has been previously observed in the hippocampus and entorhinal cortex, with a complex, non-one-to-one relationship with oscillatory state. We test the hypothesis of altered state-based information processing in the pilocarpine model, analyzing how neurons in these regions store and exchange information during slow and theta oscillations.

Methods: We induced status epilepticus (SE) on 6 male Wistar with pilocarpine injection. At least 8 weeks after SE induction, we performed acute recordings under anesthesia. Two 32-site silicon probes (NeuroNexus) were implanted in the dorsal hippocampus and medial entorhinal cortex (mEC). Recording sessions were divided into brain states of theta (THE) and slow oscillation (SO) periods. We used KLUSTAKWIK for spike sorting. Five control animals were used for comparison.

Results: We find that low-level information processes (neuronal firing, information storage, and information sharing) remained organized into substates in epileptic conditions. However, aspects of their internal composition and organization through time are disrupted, brain state constraints are changed, and overall organization is shifted towards a regime of disorder, all in a brain region dependent manner. Computational hubs are still present as well but become more rigid as compared to control.

Conclusions: We equate the storage and sharing of information to low level, or primitive, information processing at the algorithmic level, the theoretical intermediate level between structure and function. We propose that the alteration of information processing at an algorithmic level may be a mechanism behind the emergent and widespread co-morbidities associated with epilepsy, and perhaps other neurological disorders. Many different structural reorganizations can produce identical alterations at the algorithmic level, making it an ideal level of analysis to investigate the mechanisms of co-morbidities.

Funding: Please list any funding that was received in support of this abstract.: W.C. is funded through the M-GATE program, who has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 765549. T.M was funded through Aix-Marseille Universite. P.P.Q. acknowledges support from FRM, FFRE and CURE Epilepsy Taking Flight Award. D.B. has benefited for this work from support provided by the French Agence Nationale pour la Recherche (ERMUNDY, ANR-18-CE37-0014-02) and by the University of Strasbourg Institute for Advanced Study (USIAS) for a Fellowship, within the French national programme “Investment for the future” (IdEx-Unistra). C.B. is funded through ANR 19-CE14-0036-01.