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 susceptibility of the immature brain involves nonsynaptic mechanisms. Extracellular recordings were obtained from area CA1 of the hippocampus and from the dentate gyrus in slices from rats 6-9 days old (1 wk), 11-15 days old (2 wk), 19-23 days old (3 wk), and >60 days old (adult). These slices were exposed to a low-[Ca²⁺] solution that included the calcium chelator, ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), and the excitatory amino acid antagonists, 6,7-dinitroquinoxaline-2,3-dione (DNQX) and DL-2-amino-5-phosphonopentanoic acid (AP-5). They were also exposed to a hyposmolar low-[Ca²⁺] solution (diluted with 20% H₂O by volume), which induced or intensified the bursting. The propensity for nonsynaptic bursting and the characteristics of the bursts were compared between age groups. 2. The 1-wk group showed no bursting activity under any treatment condition in either CA1 or the dentate gyrus. Bursting occurred more frequently in the 2- and 3-wk groups than in the adult group in both CA1 and the dentate gyrus. 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 spikes per burst was also higher in slices from immature rats in dilute low- [Ca²⁺] solution. These findings demonstrate that nonsynaptic bursting 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 membrane-impermeable solute mannitol abolished nonsynaptic bursting in all 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 nonsynaptic epileptiform activity. The epileptiform bursts in CA1 were also more robust in the immature animals. Therefore the lower seizure threshold 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 stages of development in children.