Loss of dendritic inhibition in the hippocampus after repeated early-life hyperthermic seizures in rats.
Seizures are relatively common in children and are a risk factor for subsequent temporal lobe epilepsy. To investigate whether early-life seizures themselves are detrimental to the proper function of the adult brain, we studied whether dendritic excitation and inhibition in the hippocampus of adult rats were altered after hyperthermia-induced seizures in immature rats. In particular, we hypothesized that apical dendritic inhibition in hippocampal CA1 pyramidal cells would be disrupted following hyperthermia-induced seizures in early life. Seizure rats were given three hyperthermia-induced seizures per day for three days from postnatal day (PND) 13 to 15; control rats were handled similarly but not heated. At PND 65-75, paired-pulse inhibition in area CA1 was evaluated under urethane anesthesia, using CA3 and medial perforant path (MPP) stimulation to excite the proximal and distal apical-dendrites, respectively, and the evoked field potentials were analyzed by current source density. There was no difference in the CA1 response to single-pulse stimulation of CA3 or MPP. In control rats, a high-intensity CA3 stimulus inhibited a subsequent MPP-evoked CA1 distal dendritic excitatory sink, and the inhibition at 150-200 ms was blocked by a GABA(B) receptor antagonist. Seizure as compared to control rats showed a decrease in a CA3-evoked inhibition of the CA1 distal dendritic excitation, 30-400 ms after the CA3 stimulus. In addition, seizure as compared to control rats showed a reduced early (20-80 ms) inhibition of a CA1 mid-apical dendritic sink following paired-pulse CA3 stimulation. In conclusion, long-term alterations in dendritic inhibition in CA1 were found following early-life seizures.
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
Richard
R
Boyce
L Stan
LS
Leung
D000367:Age Factors; D000818:Animals; D003712:Dendrites / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D006979:Hyperthermia, Induced / Q000009:adverse effects* / Q000379:methods; D009433:Neural Inhibition / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D012008:Recurrence; D012640:Seizures / Q000209:etiology / Q000503:physiopathology*; D013997:Time Factors