engleski

Excitotoxic cell loss in the mouse hippocampus following sustained electrical stimulation of the perforant path

Seizure-induced neuron loss has been studied in the rat dentate gyrus following sustained electrical stimulation of the perforant path (Sloviter RS, 1987, Science 235:73-76). In the present study, we have transferred this well established model of hippocampal excitotoxicity to the mouse. This will make it possible to use transgenic mouse mutant resources to study the molecular and cellular mechanisms underlying seizure-induced pathology and pathophysiology. Adult C57Bl6 mice were anesthetized with urethane, an electrode was positioned stereotaxically in the angular bundle, and stimuli were delivered for 24h (continuous 2 Hz, paired-pulse stimulation with 10 sec trains of single stimuli at 20 Hz once per minute). A recording electrode was placed in the granule cell layer of the dentate gyrus. Stimulation evoked granule cell field potentials and population spikes in the ipsi- as well as the contralateral dentate gyrus. Following 24 hr of stimulation, during which granule cell epileptiform discharges were evoked, cellular changes were studied using Nissl staining, immunostaining for the neuronal marker NeuN, and parvalbumin, a marker for a subset of GABAergic inhibitory neurons. 4 days after stimulation, more than 80% of the neurons normally found in the hilus of the dentate gyrus were lost. In addition, the number of detectable parvalbumin-immunoreactive neurons in the dentate gyrus was significantly decreased. These data replicate the results previously reported in rats using the same high frequency stimulation protocol. We will now use high frequency stimulation of transgenic mice to genetically dissect the mechanisms underlying structural changes and cell loss in the dentate gyrus.

mouse hippocampus; electical stimulation; perforant path

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