Hippocampal Metaplasticity Induced by Deficiency in the Extracellular Matrix Glycoprotein Tenascin-r.
From: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, D-20251 Hamburg, Germany.
The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publish Date: May 2007
- ISSN: 1529-2401
- Volume: 27
- Issue: 22
- Pages: 6019-28
- Medium: Internet
- Language: English
- Citation (JAMA): Bukalo Olena, Schachner Melitta, Dityatev Alexander, et al. Hippocampal Metaplasticity Induced by Deficiency in the Extracellular Matrix Glycoprotein Tenascin-r.. J. Neurosci. May 2007;27:6019-28
Abstract
Predisposition of synapses to undergo plastic changes can be dynamically adjusted according to the history of synaptic activity (i.e., synapses are metaplastic). In search of a molecular mechanism underlying metaplasticity, we investigated mice deficient in the glycoprotein tenascin-R (TNR), based on the observations that this mutant exhibits elevated basal excitatory synaptic transmission and reduced perisomatic GABAergic inhibition. TNR is a major extracellular matrix glycoprotein of the CNS and carries the HNK-1 carbohydrate (human natural killer cell glycan), which has been identified as the functional epitope mediating regulation of GABAergic transmission via GABA(B) receptors. Here, we used patch-clamp recordings in hippocampal slices to determine the critical levels of postsynaptic neuron depolarization necessary for induction of long-term potentiation (LTP) at CA3-CA1 synapses and found that deficiency in TNR leads to a metaplastic increase in the threshold for induction of LTP. Reconstitution of slices from TNR-deficient mice with an HNK-1 glycomimetic or pharmacological treatment with either a GABA(A) receptor agonist, a GABA(B) receptor antagonist, an L-type voltage-dependent Ca2+ channel blocker, or an inhibitor of protein serine/threonine phosphatases restored LTP to the levels seen in wild-type mice. We propose that a chain of events initiated by reduced GABAergic transmission and proceeding via Ca2+ entry into cells and elevated activity of phosphatases mediates homeostatic adjustment of hippocampal plasticity in the absence of TNR. These data uncover a novel mechanism by which an extracellular matrix molecule and its associated carbohydrate provide conditions beneficial for induction of LTP in the CA1 region of the hippocampus.
Mesh Headings (Keywords): Animals, Extracellular Matrix Proteins, Hippocampus, Long-Term Potentiation, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity, Tenascin
Check for Full Text / PubMed Unique Identifier (PMID): 17537973
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