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
Ak. Saghatelyan et al., 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, EUR J NEURO, 12(9), 2000, pp. 3331-3342
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.