Enhanced cortical and hippocampal neuronal excitability in mice deficient in the extracellular matrix glycoprotein tenascin-R.

Mice deficient in the extracellular matrix protein tenascin-R (TN-R-/- mice) show several indices of impaired perisomatic inhibition in hippocampal slices. The present study examined electroencephalograms (EEGs) and auditory-evoked potentials (AEPs) in freely moving TN-R-/- and wild-type control mice, focusing on the hippocampal CA1 field and cerebral cortex. TN-R-/- mice expressed normal high-frequency oscillations (ripples) in CA1 and only a slight reduction of peak theta frequency. In contrast, their hippocampal gamma oscillations were significantly enhanced in amplitude. Also, the amplitude of the cortical EEG of TN-R-/- mice was increased over a wide frequency range. The amplitude of cortical and, to a lesser degree hippocampal, AEPs was clearly enhanced in TN-R-/- mice. In addition, response habituation to repeated sound stimuli was significantly attenuated in TN-R-/- mice. These findings indicate that tenascin-R is involved in the regulation of certain inhibitory mechanisms in the intact brain.