Early impairment in dentate pattern separation in a rodent model of temporal lobe epilepsy.

Ewell, L. A.; Ramezani, A.; Suarez, G.; Piatti, V. C.; Lam, V.; Mills, T. G.; McGinness, A.; Kuk, R.; Ukai, M.; Schlenner, A.-L.; Leutgeb, S.; Leutgeb, J. K.

doi:10.1101/2025.11.12.688087

bioRxiv · 10.1101/2025.11.12.688087

Early impairment in dentate pattern separation in a rodent model of temporal lobe epilepsy.

Ewell, L. A.·Ramezani, A.·Suarez, G.·Piatti, V. C.·Lam, V.·Mills, T. G.·McGinness, A.·Kuk, R.·Ukai, M.·Schlenner, A.-L.·Leutgeb, S.·Leutgeb, J. K.

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Abstract

The dentate gyrus of the hippocampal formation utilizes sparse neural coding to support memory formation. In temporal lobe epilepsy (TLE), the dentate undergoes extensive restructuring, including loss of local inhibition. It is unknown how circuit changes impact dentate network computations in awake behaving animals. Here we perform high-density tetrode recordings from the dentate in male rats treated with systemic kainic acid (KA) to induce TLE. In KA-treated rats, dentate spatial representations were less precise at the single neuron level, however the stability of the spatial code in representing repeated visits to the same location was retained at the population level. Despite spared spatial representation, the network computations for pattern separation were disrupted. The reorganized dentate network in KA-treated rats generated less distinct population activity patterns for different environments, specifically as a result of impaired rate-remapping. Changes in network computations paralleled impairments in a dentate-dependent memory task, potentially providing a link between altered pattern separation and behavioral discrimination. These deficits were present in animals with confirmed dentate circuit reorganization that had not yet developed spontaneous seizures - suggesting that the dentate network changes underlying altered rate-remapping and impaired dentate-dependent memory occur early in epileptogenesis.

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Ewell, L. A., Ramezani, A., Suarez, G., Piatti, V. C., Lam, V., Mills, T. G., McGinness, A., Kuk, R., Ukai, M., Schlenner, A.-L., Leutgeb, S., Leutgeb, J. K.. 2025-11-12. Early impairment in dentate pattern separation in a rodent model of temporal lobe epilepsy.. https://doi.org/10.1101/2025.11.12.688087

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