Reduced perisomatic inhibition, increased excitatory transmission, and impaired long-term potentiation in mice deficient for the extracellular matrix glycoprotein tenascin-R.
The role of the extracellular matrix molecule tenascin-R (TN-R) in regulation of synaptic transmission and plasticity in the CA1 region of the hippocampus was studied using mice deficient in expression of this molecule. The mutant mice showed normal NMDA-receptor-mediated currents but an impaired NMDA-receptor-dependent form of long-term potentiation (LTP) as compared to wild-type 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 transmission in mutants could involve modulation of inhibition, since TN-R and its associated carbohydrate HNK-1 decorate perisomatic interneurons. Indeed, the amplitudes of unitary perisomatic inhibitory currents were smaller in mutants compared to wild-type mice. Thus, our data show that a deficit in TN-R results in reduction of perisomatic inhibition and, as a consequence, in an increase of excitatory synaptic transmission in CA1 to the levels close to saturation, impeding further expression of LTP.
Saghatelyan
A K
AK
Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, Hamburg, D-20246, Germany.
Dityatev
A
A
Schmidt
S
S
Schuster
T
T
Bartsch
U
U
Schachner
M
M
D000818:Animals; D018959:CD57 Antigens / Q000378:metabolism; D006023:Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D019063:Tenascin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D018959:CD57 Antigens; D006023:Glycoproteins; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D019063:Tenascin; C074638:tenascin R