Neuronal firing patterns of higher order thalamocortical neurons during Inter-ictal absence seizure transition: Potential Implications for Loss of Consciousness
Purpose: Thalamocortical (TC) neurons play a critical role in absence-related generalized spike-and-wave discharges (SWD) being recruited into a highly synchronised rhythmic firing pattern which blocks the normal function of first order (FO) thalamic nuclei to transmit primary sensory information. However, this alone is unlikely to explain the loss of consciousness experienced by patients. Little information exists about the involvement of higher-order (HO) TC neurons, which relay corticocortical signals and play an important role in the integration of sensorimotor information, attention and cognition.
Method: Single-cell recordings of TC neurons were made in vivo, under neurolept anaesthesia, along with EEG recording of the related sensorimotor cortex, in adult male Generalised Absence Epilepsy Rats from Strasbourg (GAERS)(n=13). Firing patterns in the posterior(Po; n=39) thalamic group were compared with the ventrobasal(VB; n=20) thalamus (i.e. the principle somatosensory HO and FO nuclei respectively).
Results: Interictally the median percentage of burst firing/cell was higher in Po cells (15% vs. 5%, p=0.07), with a higher median maximal number of action potentials per burst (5 vs. 4, p=0.02). With the ictal transition both neuronal types switched early (240±12 vs. 210±8 msecs prior to seizure onset, p=0.85) to a rhythmic firing pattern that was highly synchronised with the EEG SWDs and had a high firing probability (0.76±0.04 vs. 0.68±0.06, p=0.31). The firing of the Po cells in relation to each SWD was earlier (-19±2 vs. -12±3 msecs, p=0.01) and showed more burst firing (median/cell 50% vs. 30%, p<0.001).
Conclusions: Somatosensory HO TC neurons are involved in the absence-related firing pattern as early and as extensively as their FO counterparts, with more prominent burst firing. These features would be expected to result in a disruption of the function of HO TC neurons to relay and integrate corticocortical information, and therefore may play a mechanistic role in the loss of consciousness.