Figure 5. Extracellular GABA Decreases in the Seizure Onset Area Several Hours Before a Spontaneous Seizure.

(A–D) Hourly fluctuations in hippocampal GABA levels with respect to a spontaneous seizures, starting 5 hours before a seizure and ending 5 hours after. Traces from epileptic (methionine sulfoximine [MSO]–infused; n = 3) rats are shown at the top; traces from the same time points in nonseizing (phosphate buffered saline [PBS]–infused; n = 3) rats are shown at the bottom. Seven spontaneous seizures that were >6 hours away from each other were identified, and the GABA level at 5 hours before the seizure was normalized to 1 with the subsequent concentrations expressed as a value relative to this. Compared to the baseline value at 5 hours before the seizure, GABA decreased significantly in the seizure onset area (MSO ipsilateral B) 3 hours before the seizure (p < 0.05), after which the level rose back to baseline. This was followed by a second, continuous decrease starting at the time of the seizure and ending 3 hours after (p < 0.05), with return to baseline 4 hours after seizure. In the seizure-propagated hippocampus (A, MSO contralateral), GABA decreased significantly from baseline starting 1 hour after the seizure (p < 0.05; figure 4A) and remaining below baseline at a level that approached significance for an additional 2 hours (p = 0.06; figure 4A). The GABA level was not significantly different from baseline during any hour in corresponding samples from 7 time-matched samples from nonepileptic rats (figure 4, C and D). Values are expressed as mean ± SEM.