Abstracts

Rationale: An understanding of how seizure activity may be initiated or spread requires an understanding of the nature of the circuits involved. The midline thalamus has been hypothesized to act as a distributor of seizure activity throughout the various structures in the limbic network, due to its widespread excitatory input to those structures. We sought to characterize the role of the midline thalamus in the induction or spread of seizure activity in two different circuits: (a) the subiculum-prefrontal cortex connection, and (b) the piriform cortex-entorhinal cortex connection. These pairings were chosen because the first (stimulation) site has well-described connections both to the target site and the midline thalamic region, and because they are sites with relevance to limbic seizure models. Methods: In urethane anesthetized rats, evoked local field potentials were obtained at 7 Hz in either the entorhinal cortex or the prefrontal/cingulate cortex by stimulation of the piriform cortex or subiculum, respectively. Responses were characterized as having an early (0-30 ms latency) and late (30-55 ms) component. Seizures were induced by repeated 20 Hz stimulations. Once seizures became stable, tetrodotoxin (TTX) was injected into the midline thalamic nuclei to inactivate thalamic activity. The effects of the inactivation were measured for both the seizure durations and the evoked potentials until recovery. Results: Inactivation of the midline thalamus resulted in a profound reduction in seizure duration. This simultaneously caused a reduction in the late (likely polysynaptic and thalamically-mediated) components of the field potentials in both circuits. The early components of the response, which were likely direct monosynaptic responses from the stimulation to the recording site, were unchanged. While the technique of attenuating limbic seizures through thalamic modulation has been shown previously, its use here, in conjunction with simultaneous field potential recordings, provides additional insight into why that change occurs. Conclusions: These results suggest that in this model of limbic seizures a convergence of several excitatory pathways onto a target site may be necessary to drive a region into a seizure. In these experiments, the excitation diverged from the stimulation site to the target region and the thalamus, and these pathways then converged again on the target site to provide an enhanced excitatory drive. Excitation from the stimulation site alone was insufficient to push the target site into a seizure. Thus, a role of the midline thalamus, as a component of a divergent-convergent signal amplification circuit, may be to provide the additional excitatory input necessary to induce and spread seizures. These results also emphasize the widespread influence that the midline thalamus has throughout the limbic network.