Abstracts

Rationale: In rats, the period of maximal seizure susceptibility does not coincide with the first postnatal (P) week when inhibition is minimal or lacking but just prior to the second and during the third weeks of postnatal life, a time when NMDA receptors are transiently overexpressed. Methods: We microinfused NR1 antisense oligodeoxynucleotides (ODNs) into the lateral ventricle, hippocampus or parietal cortex of 7- and 13-day-old rats for 2-3 days in order to investigate molecular and anatomical mechanisms underlying the increased susceptibility of the developing brain to hyperexcitability. Results: Behavioral onset to kainate-induced seizures was unaltered at both ages but long bouts of lying on one side with bilateral body tonus was highly reduced after ventricle or cortical knockown in the older P13 age group. This behavior is typically observed in control animals and appears correlated with seizure-induced changes in cortical morphology. The electroencephalogram (EEG) showed many cortical spikes but traces lacked high synchronous activity detected in controls. TUNEL and silver impregnation methods revealed selective staining of CA1 neurons throughout the ipsilateral hippocampus in the P13 but not P7 age group. Immunohistochemistry confirmed specificity such that NR1 but not NR2 receptor protein was reduced ipsilaterally. Conclusions: Overexpression of NR1 receptor subunits in hippocampus appears necessary for age-dependent survival of CA1 but not CA3 neurons following status epilepticus. Expression of NR1 receptor subunits in sensory/motor cortex may mediate body tonus but not subconvulsive automatisms such as scratching, head shakes and mouth movements. Supported by NIH- NS 38069-02