Implication of Anterior Nucleus of the Thalamus in Mesial Temporal Lobe Seizures

• Published in: Neuroscience Vol. 418; pp. 279 - 290
• Main Authors: Sherdil, Ariana, Coizet, Véronique, Pernet-Gallay, Karin, David, Olivier, Chabardès, Stephan, Piallat, Brigitte
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 15.10.2019; Elsevier - International Brain Research Organization
• Subjects: anterior nucleus of the thalamus; Life Sciences; mesial temporal lobe epilepsy; nonhuman primate; single unit recording; DG; MTLE; MTL; PNC; ANT; BL; nonhuman primate; anterior nucleus of the thalamus; FR; mesial temporal lobe epilepsy; PSTH; DBS; NHP; HPC; single unit recording
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2019.06.018

Deep brain stimulation of the anterior nucleus of the thalamus has been proposed as novel therapy to treat intractable epilepsy. To optimize this approach, we proposed to study the involvement of this nucleus in a non-human primate model of mesial temporal lobe seizure. Two macaques were implanted with one chronic electrode into the hippocampus allowing to monitor the ictal activity. Neurons of the anterior nucleus of the thalamus were recorded with a microelectrode inserted acutely. To induce seizures, penicillin was injected into the hippocampus and neuronal activities of the anterior nucleus were analyzed during ictal and interictal periods. The effects of the chemical neuromodulation of the anterior nucleus on the ictal hippocampal activities were studied and electron microscopy analysis was carried out to study morphological modifications induced in the anterior nucleus of the thalamus. Our results demonstrate that the anterior nucleus of the thalamus is directly involved in the pathophysiology of induced seizures since: (1) Electrophysiological study showed an heterogenous excitation during seizure characterized by the appearance of 2 types of neuronal firing response; (2) chemical neuromodulation of the anterior nucleus of the thalamus changed the severity of seizures; (3) morphological modification of the ultrastructure as well as a reduction of synapse density were observed within the ipsilateral anterior nucleus of the thalamus. This study demonstrates that the anterior nucleus of the thalamus is part of the epileptic network activated during temporal lobe seizures and suggests that this nucleus would be valid target for seizure control using deep brain stimulation. •Mesial temporal lobe epilepsy is the most common focal epilepsy, often associated with drug resistance.•The ANT is actively involved during interictal and ictal periods in a non-human primate model of mesial temporal lobe seizures.•This implication is heterogeneous, since some neurons were activated by ictal events whereas others were inhibited, and associated with morphological reorganizations.•The implication of anterior nucleus of the thalamus in the pathophysiology of MTLE supports that its electrical stimulation could therefore be an effective and safe treatment for MTLE.