Excitatory amplification through divergent–convergent circuits: The role of the midline thalamus in limbic seizures

IntroductionThe midline thalamic nuclei are an important component of limbic seizures. Although the anatomic connections and excitatory influences of the midline thalamus are well known, its physiological role in limbic seizures is unclear. We examined the role of the midline thalamus on two circuits that are involved in limbic seizures: (a) the subiculum–prefrontal cortex (SB–PFC), and (b) the piriform cortex–entorhinal cortex (PC–EC).MethodsEvoked field potentials for both circuits were obtained in anesthetized rats, and the likely direct monosynaptic and polysynaptic contributions to the responses were identified. Seizures were generated in both circuits by 20 Hz stimulus trains. Once stable seizures and evoked potentials were established, the midline thalamus was inactivated through an injection of the sodium channel blocker tetrodotoxin (TTX), and the effects on the evoked responses and seizures were analyzed.ResultsInactivation of the midline thalamus suppressed seizures in both circuits. Seizure suppression was associated with a significant reduction in the late thalamic component but no significant change in the early direct monosynaptic component. Injections that did not suppress the seizures did not alter the evoked potentials.ConclusionsSuppression of the late thalamic component of the evoked potential at the time of seizure suppression suggests that the thalamus facilitates seizure induction by extending the duration of excitatory drive through a divergent–convergent excitatory amplification system. This work may have broader implications for understanding signaling in the limbic system.

Research highlights
► We examine the role of the midline thalamic region which may have a major role in limbic seizures.
► Inactivation of midline thalamus with a sodium channel blocker inhibits seizures induced by electrical stimulation of limbic sites.
► Inactivation of the medial dorsal nucleus blocks seizures and reduces the thalamic component of the evoked responses.
► Findings suggest that medial dorsal nucleus=s role is to prolong excitatory drive as part of a divergent-convergent circuit.