Reduced perisomatic inhibition, increased excitatory transmission, and impaired long-term potentiation in mice deficient for the extracellular matrixglycoprotein tenascin-R

The role of the extracellular matrix molecule tenascin-R (TN-R) in regulati on of synaptic transmission and plasticity in the CA1 region of the hippoca mpus was studied using mice deficient in expression of this molecule. The m utant mice showed normal NM DA-receptor-mediated currents but an impaired N M DA-receptor-dependent form of long-term potentiation (LTP) as compared to wildtype littermates. Reduced LTP in mutants was accompanied by increased basal excitatory synaptic transmission in synapses formed on CA1 pyramidal neurons. A possible mechanism for increased excitatory synaptic transmissio n in mutants could involve modulation of inhibition, since TN-R and its ass ociated carbohydrate HNK-1 decorate perisomatic interneurons. Indeed, the a mplitudes of unitary perisomatic inhibitory currents were smaller in mutant s compared to wild-type mice. Thus, our data show that a deficit in TN-R re sults in reduction of perisomatic inhibition and, as a consequence, in an i ncrease of excitatory synaptic transmission in CA1 to the levels close to s aturation, impeding further expression of LTP.