Abstracts

Rationale: A growing body of experimental evidence indicates that absence seizures arise from a cortical focus in the somatosensory neocortex.1,2 However the intracortical localization of the seizure generator is still unknown. Previous work has demonstrated that seizures in Generalized Absence Epilepsy Rats from Strasbourg (GAERS) arise from a normal 5-9 Hz somatosensory rhythm, which is also present in non-epileptic control (NEC) rats.3 The aim of the present study was to characterize at the single-cell level the epileptogenic focus.Methods: Single-cell juxtacellular recordings of cortical neurons and extracellular field recordings were made in vivo, under neurolept anaesthesia, along with EEG recording of the related sensorimotor cortex in adult male GAERS (n=19) and NEC rats (n=11). Ictal and interictal firing patterns were compared between cells in the lateral somatosensory cortex (S2, n=15) vs. those in the more superior somatosensory cortex (S1, n=42) and in the insular cortex (IC, n=10), as well as between cells in the different cortical layers (i.e. layers V (n=31), VI (n=15) and superficial layers II-IV, n=20). The location of the recorded cells was confirmed at the end of each experiment by juxtacellular labelling with neurobiotin.Results: In GAERS the median percentage of burst firing/cell was higher interictally in S2 (20%) than in S1 (5%) or IC (5%) (p=0.04), and ictally (S2=64%, S1=35%, IC=41%, p=0.09). Ictally cells from the S2 fired earlier with each spike-and-wave (SW) complex (median, S2=-37 vs. S1=-16 and IC=-27 ms, p=0.03). Layer VI cells fired earlier ictally than layer V or superficial layer cells (VI=-36, V=-14, II-IV=-27 msecs, p=0.007) with more burst firing (70%, 40%, 20%, p=0.01). The ictal firing probability/SW complex was less for the superficial layer cells than for Layer V or VI cells (II-IV=37%, V=90%, VI=90%, p=0.003). Mutivariate analysis confirmed that both the brain region and the cell layer were independently predictive of ictal firing timing, but only the layer for ictal bursting and firing probabilities. Importantly, a population of cells were identified within layer V and VI, focused around S2, which continued firing in a rhythmic manner interictally. These rhythmic cells were also seen in NEC rats.Conclusions: Layer VI cells in S2 show increased burst firing interictally and ictally in GAERS, and fire earlier with each SW discharge than cells in other layers and regions. This is consistent with these cells being the focal “drivers” of the seizures. Additionally a population of apparently inherently rhythmic cells were identified in the deep cortical layers focused around the S2 region in both GAERS and NEC rats which may be the source of the physiological somatosensory 5-9 Hz. rhythm which subsequently triggers the seizures in the epileptic animals.