INCREASED PROPENSITY FOR NONSYNAPTIC EPILEPTIFORM ACTIVITY IN IMMATURE RAT HIPPOCAMPUS AND DENTATE GYRUS

1. Low-[Ca2+] bursting was studied in hippocampal slices from immature and adult rats to test the hypothesis that the increased seizure susc eptibility of the immature brain involves nonsynaptic mechanisms. Extr acellular recordings were obtained from area CA1 of the hippocampus an d from the dentate gyrus in slices from rats 6-9 days old (1 wk), 11-1 5 days old (2 wk), 19-23 days old (3 wk), and >60 days old (adult). Th ese slices were exposed to a low-[Ca2+] solution that included the cal cium chelator, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-te traacetic acid (EGTA), and the excitatory amino acid antagonists, 6,7- dinitroquinoxaline-2,3-dione (DNQX) and DL-2-amino-5-phosphonopentanoi c acid (AP-5). They were also exposed to a hyposmolar low-[Ca2+] solut ion (diluted with 20% H2O by volume), which induced or intensified the bursting. The propensity for nonsynaptic bursting and the characteris tics of the bursts were compared between age groups. 2. The 1-wk group showed no bursting activity under any treatment condition in either C A1 or the dentate gyrus. Bursting occurred more frequently in the 2- a nd 3-wk groups than in the adult group in both CA1 and the dentate gyr us. 3. In CA1 the duration of the bursts was longer in the 2- and 3-wk groups as compared with the adult group. The number of population spi kes per burst was also higher in slices from immature rats in dilute l ow-[Ca2+] solution. These findings demonstrate that nonsynaptic bursti ng in area CA1 is more robust in tissue from immature rats than adults . 4. Bathing the slices in a low-[Ca2+] solution that contained the me mbrane-impermeable solute mannitol abolished nonsynaptic bursting in a ll experiments regardless of age. 5. These results show that there is a developmental window at 2-3 wk in the rat where both the CA1 area of the hippocampus and the dentate gyrus are more susceptible to nonsyna ptic epileptiform activity. The epileptiform bursts in CA1 were also m ore robust in the immature animals. Therefore the lower seizure thresh old known to occur in the immature brain is present even when chemical synaptic transmission is absent. These findings may have implications for epileptic disorders that have a predilection for certain early st ages of development in children.