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 from the hippocampus. The striking presence of HNK-1, a carbohydrate expressed by neural adhesion molecules, on perisomatic interneurons and around somata of CA1 pyramidal neurons led us to apply monoclonal HNK-1 antibodies to acute murine hippocampal slices. Injection of these antibodies decreased GABAA 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 accompanied by an increase in the coefficient of variation of pIPSC amplitude, number of failures and changes in frequency but not amplitude of miniature IPSCs, suggesting that HNK-1 antibodies reduced efficacy of evoked GABA release. HNK-1 antibodies did not affect pIPSCs in knock-out mice deficient in the extracellular matrix molecule tenascin-R which carries the HNK-1 carbohydrate as analysed by immunoblotting in synaptosomal fractions prepared from the CA1 region of the hippocampus. For control, HNK-1 antibody was applied to acute sections of mice deficient in the neural cell adhesion molecule NCAM, another potential carrier of HNK-1, and resulted in decrease of pIPSCs 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 was 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 carbohydrate modulate perisomatic inhibition and synaptic plasticity in the hippocampus.
Saghatelyan
A K
AK
Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany.
Gorissen
S
S
Albert
M
M
Hertlein
B
B
Schachner
M
M
Dityatev
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018959:CD57 Antigens / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008564:Membrane Potentials / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology*; D009500:Neutralization Tests; D010320:Parvalbumins / Q000032:analysis; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D009435:Synaptic Transmission / Q000276:immunology; D019063:Tenascin / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018959:CD57 Antigens; D016326:Extracellular Matrix Proteins; D019006:Neural Cell Adhesion Molecules; D010320:Parvalbumins; D011963:Receptors, GABA-A; D019063:Tenascin; C074638:tenascin R