Abstracts

RATIONALE: During development, synchronized pre-and post synaptic activity is critical for refining synaptic connection between axons and their appropriate targets. To determine whether a prolonged seizure, via intense synchronized neuronal activation, will alter dendritic branching pattern in the developing hippocampus, we used rapid golgi method to visualize and quantify basal dendrites of CA3 pyramidal neurons following kainate (KA)-induced seizures in the immature brain. METHODS: P15 rats were injected either with KA(3mg/kg)or PBS. At P20, animals were decapitated, and the brains were immersed in Golgi-Cox solution for 4-6 weeks. Camera lucida drawings of 32 neurons each from 2 control and 2 KA animals were made under 40 X objective (magnified 240 x actual size). Primary, secondary and tertiary branches of basal dendrites of CA3 pyramidal neurons were separately counted and summed to give total number of branches. RESULTS: Compared to controls, hippocampal neurons of animals that experienced kainate induced status epilepticus at P15 and sacrificed at P20 had a significantly less number of total branches (control 23.7 b1.03 vs.kainate 20.3 b0.96, p=0.023). This signifant difference was due to the loss of complexity of tertiary branching in KA-treated animals(8.5 vs. 6, p=0.025) since no significant difference in the number of primary branches and secondary branches were found. From the end of the soma to the tip of the longest basal dendrite, the actual length of a typical CA3 hippocampal pyramidal neuron is between 100 and 150 micrometers. CONCLUSIONS: Early life kainate-induced status epilepticus causes a morphological change in CA3 hippocampal pyramidal neurons as shown by the decrease in the total number of basal dendritic branches and loss of complexity in tertiary branching patterns. While immature hippocampal neurons are resistant to seizure-induced cell death, they may be uniquely vulnerable to structural alteration caused by excessive synaptic activity during development. (Supported by K08NS-02068(SK)and RO1NS-31718).