Hyperthermia induces age-dependent changes in rat hippocampal excitability.

The mechanisms underlying the generation of febrile seizures are poorly understood. This study investigated hyperthermia-induced changes in the hippocampus, a structure implicated in febrile seizures. It was hypothesized that neuronal excitability in the hippocampus changes with increasing temperature, and that this change is different in adult as compared with immature rats. Adult and immature (15-17 days postnatal) male rats were studied under urethane anesthesia during normothermia, moderate hyperthermia (38-39.5 degrees C), and severe hyperthermia (>39.5 degrees C). Paired-pulse inhibition of the orthodromically activated population spikes in the dentate gyrus and cornu ammonis 1 region of the hippocampus (CA1), two structures within the hippocampus, was measured after stimulation of the medial perforant path and Schaffer collaterals, respectively. In the adult rat, paired-pulse inhibition was increased in the dentate gyrus during moderate and severe hyperthermia but decreased in CA1 during severe hyperthermia (all p values < 0.05). In the immature rat, paired-pulse inhibition was unchanged in the dentate gyrus but decreased in CA1 during moderate hyperthermia (p < 0.05). We suggest that hyperthermia contributes to seizure susceptibility in the immature hippocampus by decreasing CA1 inhibition. In the adult rat, a decrease in CA1 inhibition requires a higher degree of hyperthermia, and hippocampal seizure generation is opposed by an increase in dentate gyrus inhibition.