Post-traumatic epilepsy is a common outcome of severe traumatic brain injury (TBI). The development of spontaneous seizures after traumatic brain injury generally follows a latent period of little to no symptoms. The series of events occurring in this latent period are not well understood. Additionally, there is no current treatment to prevent the development of epilepsy after TBI (i.e. antiepileptogenics). One cell signaling pathway activated in models of TBI and in models of epilepsy is the mammalian target of rapamycin (mTOR). mTOR activity is sustained for weeks after the initial insult in models of TBI, and the inhibition of mTOR using rapamycin has shown promising pre-clinical outcomes in rodent models. This makes rapamycin an ideal therapeutic to test various outcomes associated with epileptogenesis after TBI. The results from this study suggest that rapamycin treatment after controlled cortical impact reduces aberrant axonal sprouting of ipsilateral dentate granule cells, prevents increased neurogenesis in the subgranular zone, and differentially alters phasic and tonic inhibition in dentate granule cells. However, rapamycin treatment did not prevent all forms of axon sprouting in the dentate gyrus or cell loss in selected regions of the hippocampus. Collectively these results support a role of mTOR activity in both excitatory and inhibitory plasticity in the mouse dentate gyrus after TBI.

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Le gyrus denté occupe une position clé au sein du lobe temporal des mammifères en constituant le point de contrôle entre le système néocortical et le système hippocampique. Considéré comme la porte de l'hippocampe, le gyrus denté filtre les activités excitatrices en provenance du cortex entorhinal grâce à la décharge éparse des cellules granulaires. Ce type de codage neuronal lui confère également un rôle déterminant dans les mécanismes de l'apprentissage et de la mémoire lors de la distinction d'évènements similaires mais différents, en permettant la décorrélation des patrons d'activité corticale. Grâce à un ensemble de propriétés structurales et fonctionnelles, les cellules granulaires du gyrus denté génèrent des évènements synaptiques extrêmement rapides restreignant leur fenêtre temporelle d'intégration et leur permettant de jouer le rôle de détecteurs de coïncidence. Au cours d'une épilepsie du lobe temporal (ELT), l'hippocampe présente d'importantes altérations de codage neuronal qui pourraient participer aux troubles cognitifs décrits chez les patients et les modèles animaux. Dans ces conditions pathologiques, les axones des cellules granulaires du gyrus denté (les fibres moussues) bourgeonnent et établissent des synapses aberrantes au niveau d'autres cellules granulaires, créant ainsi un puissant réseau excitateur récurrent. Ces fibres moussues récurrentes convertissent la nature de la transmission glutamatergique car elles opèrent via des récepteurs kaïnate générant des potentiels post-synaptiques à cinétique lente, absents en condition contrôle. / The dentate gyrus plays a major role at the gate of the hippocampus, filtering incoming information from the entorhinal cortex. A fundamental coding property of dentate granule cells (DGCs) is their sparse firing. Indeed, they behave as a coincidence detector due to the fast kinetics of excitatory synaptic events restricting integration of afferent inputs to a narrow time window. In temporal lobe epilepsy (TLE), the hippocampus displays important coding alterations that may play a role in cognitive impairments described in patients and animal models. However, the cellular mechanisms remain poorly understood. In animal models of TLE and human patients, neuronal tissue undergoes major reorganization; some neurons die whereas others, which are severed in their inputs or outputs, sprout and form novel aberrant connections. This phenomenon, called reactive plasticity, is well documented in the dentate gyrus where DGC axons (the mossy fibres) sprout and create a powerful excitatory network between DGCs. We recently showed that in addition to the axonal rewiring, recurrent mossy fibres convert the nature of glutamatergic transmission in the dentate gyrus because they operate via long-lasting kainate receptor (KAR)-mediated EPSPs (EPSPKA) not present in the naive condition.