Abstracts

Rationale: The thalamus is a critical subcortical network hub containing several distinct nuclei with different functions. Temporal lobe epilepsy is a common and debilitating neurological disorder, characterized by seizures that often impair consciousness. Accumulating evidence suggests that the thalamus, as a key subcortical arousal region with connections to both hippocampus and cortex, may play a major role in modulation of suppressed cortical activity, seizure propagation and formation of corticothalamic oscillations during seizures. Methods: Multi-unit recordings of different thalamic nuclei were performed in an anesthetized rat model of limbic seizures to study peri-ictal function of the intralaminar central lateral nucleus (CL), anterior nucleus (ANT), and ventral posteromedial nucleus of the thalamus (VPM). Furthermore, juxtacellular recordings in the CL thalamus were applied to investigate single neuron activity changes during focal seizures. Neurons juxtacellularly recorded were labeled with neurobiotin for histologic recovery and all the electrode tracts were identified by histology staining with cresyl violet. Results: We found that during focal limbic seizures, multiunit activity (MUA) in the CL region decreased while MUA in the ANT increased (p < 0.05, n = 35). In both regions, neuronal firing slowly recovered during the postictal period. MUA recordings from VPM were notable for an increase in spindle waves during focal seizures which returned to baseline following the postictal period (n = 36). Consistent with decreased MUA in the CL, single-cell juxtacellular recordings from individual neurons in the CL showed decreased firing after the seizure initiation and recovery during the postictal period (n = 14). Interestingly, most neurons in CL fired with a burst pattern during seizures but fired single spikes during baseline and after recovery. Conclusions: These results suggest that different thalamic nuclei may play different roles in seizure propagation, cortical inhibition, and spindle wave oscillation formation during focal limbic seizures. At the cellular level, reduced firing rates and a burst firing mode for identified CL neurons were recorded. Considering that burst firing is a pattern similar to that found in slow-wave sleep or deep anesthesia, our findings suggest depressed arousal of the CL region of the thalamus, which may suppress the activity of the cortex. Decreased subcortical arousal could be a critical mechanism for loss of consciousness in focal temporal lobe seizures. Funding: NIH Grant R01 NS066974