Abstracts

RATIONALE: Endogenous acetylcholine (ACh) enhances epileptogenesis in immature hippocampus (Gruslin et al., 1999, Dev Brain Res 835:290-297; Psarropoulou et al, 1998 Neurosci. 82/4:1067-77). Seizure manifestation depends on the spread of epileptiform activity in the cortex, where cholinergic innervation is dense and moreover develops early in postnatal life. We therefore investigated the effects of endogenous ACh on excitatory potentials of immature cortex in vitro. METHODS: We have studied the effects of a standard dose of the AChE inhibitor eserine (10 M) on the spontaneous and evoked epileptiform synchronous discharges recorded extracellularly in the presence of 50 M bicuculline (BMI) from the deep layers of parasagittal slices of immature (postnatal days 10-31) rat cortex. RESULTS: Eserine depressed field potentials in BMI (13/19 slices, 68%), by reversibly decreasing their amplitude (by 29.5 6.6%, n=13) and duration (by 26.3 4.7%, n=11). BMI induced low rate (1 every 2-12min) interictal-like (~1s, 15/23 slices) or ictal-like (6-16s, 14/23 slices) synchronous spontaneous discharges in all slices tested. Addition of eserine increased significantly their rates of occurence (t-test, p<0.05) and/or induced discharge types not previously recorded (in BMI alone), in a total of 9/19 slices. The sensitivity of the eserine-induced discharges to muscarinic antagonists is examined. CONCLUSIONS: These results, which are qualitatively similar to our previous findings in immature hippocampus, suggest that a rise in the concentration of endogenous ACh facilitates the generation of epileptiform discharges in immature disinhibited cortex. Thus, endogenous ACh may promote seizure manifestation. At the same time, by decreasing the amplitude and/or duration of individual discharges, ACh may avert the long-term excitotoxic damage frequently associated with sustained excitatory potentials. Supported by NSERC, FRSQ.