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Site-specific hippocampal pathophysiology due to cerebral overexpression of interleukin-6 in transgenic mice
S C Steffensen1, I L Campbell, S J Henriksen
1Department of Neuropharmacology (CVN-13), Scripps Research Institute, La Jolla, CA 92037.
Abstract:
Transgenic mice expressing the cytokine interleukin-6 exhibit distinctive hippocampal interneuron pathology and behavioral seizures. Electroencephalographic recordings from these mice revealed anomalous hippocampal paroxysmal discharges and suppressed theta rhythm. Analysis of hippocampal field responses evoked by monosynaptic afferent stimulation revealed a site-specific increase in recurrent inhibition in the dentate gyrus. In addition, the cholinergic component of septohippocampal conditioning of dentate-evoked activity was absent in the transgenic mice. These results indicate that overexpression of interleukin-6 selectively disrupts cholinergic transmission by inducing a functional pathophysiology of hippocampal cholinoceptive target neurons.