The extracellular matrix molecule tenascin-R and its HNK-1 carbohydrate modulate perisomatic inhibition and long-term potentiation in the CA1 region of the hippocampus

Perisomatic inhibition of pyramidal cells regulates efferent signalling fro m the hippocampus. The striking presence of HNK-1, a carbohydrate expressed by neural adhesion molecules, on perisomatic interneurons and around somat a of CA1 pyramidal neurons led us to apply monoclonal HNK-1 antibodies to a cute murine hippocampal slices. Injection of these antibodies decreased GAB AA receptor-mediated perisomatic inhibitory postsynaptic currents (pIPSCs) but did not affect dendritic IPSCs or excitatory postsynaptic currents. The decrease in the mean amplitude of evoked pIPSCs by HNK-1 antibodies was ac companied by an increase in the coefficient of variation of pIPSC amplitude , number of failures and changes in frequency but not amplitude of miniatur e IPSCs, suggesting that HNK-1 antibodies reduced efficacy of evoked GABA r elease. HNK-1 antibodies did not affect pIPSCs in knock-out mice deficient in the extracellular matrix molecule tenascin-R which carries the HNK-1 car bohydrate as analysed by immunoblotting in synaptosomal fractions prepared from the CA1 region of the hippocampus. For control, HNK-1 antibody was app lied to acute sections of mice deficient in the neural cell adhesion molecu le NCAM, another potential carrier of HNK-1, and resulted in decrease of pI PSCs as observed in wild-type mice. Reduction in perisomatic inhibition is expected to promote induction of long-term potentiation (LTP) by increasing the level of depolarization during theta-burst stimulation. Indeed, LTP wa s increased by HNK-1 antibody applied before stimulation. Moreover, LTP was reduced by an HNK-1 peptide mimic, but not control peptide. These results provide first evidence that tenascin-R and its associated HNK-1 carbohydrat e modulate perisomatic inhibition and synaptic plasticity in the hippocampu s.