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Targeted disruption of RC3 reveals a calmodulin-based mechanism for regulating metaplasticity in the hippocampus.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Krucker, Thomas Siggins, George Robert McNamara, Robert K. Lindsley, Kristen A. Dao, Alan Allison, David W. Lecea, Luis De Lovenberg, Timothy W. Sutcliffe, J. Gregor Gerendasy, Dan D. |
| Copyright Year | 2002 |
| Abstract | We used homologous recombination in the mouse to knock-out RC3, a postsynaptic, calmodulin-binding PKC substrate. Mutant brains exhibited lower immunoreactivity to phospho-Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) but had the same synaptic density as wild type and did not exhibit a gross neuroanatomical phenotype. Basal excitatory synaptic transmission in CA1 was depressed, long-term potentiation (LTP) was enhanced, and the depressant effects of the metabotropic glutamate receptor (mGluR) agonist (RS)-3,5-dihydroxyphenylglycine was occluded compared with littermate controls. The frequency-response curve was displaced to the left, and long-term depression (LTD) could not be induced unless low-frequency stimuli were preceded by high-frequency tetani. Depotentiation was much more robust in the mutant, and only one stimulus was required to saturate LTD in primed mutant hippocampi, whereas multiple low-frequency stimuli were required in wild-type slices. Thus, ablation of RC3 appears to render the postsynaptic neuron hypersensitive to Ca(2+), decreasing its LTD and LTP thresholds and accentuating the effects of priming stimuli. We propose an mGluR-dependent CaM-based sliding threshold mechanism for metaplasticity that is governed by the phosphorylation states of RC3 and CaMKII. |
| Starting Page | 1 |
| Ending Page | 2 |
| Page Count | 2 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jneurosci.org/content/jneuro/22/13/5525.full.pdf |
| Alternate Webpage(s) | http://www.jneurosci.org/content/22/13/5525.full.pdf |
| PubMed reference number | 12097504v1 |
| Volume Number | 22 |
| Issue Number | 13 |
| Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Brain CA1 field Calmodulin Depotentiation Depressive disorder Glutamate Receptor Glutamic Acid Hippocampus (Brain) Homologous Recombination Knock-out Long-Term Potentiation Long-Term Synaptic Depression Neurons Obstruction Priming Exercise Protein Kinases Receptors, Metabotropic Glutamate Synaptic Transmission Tetany Wild Type chemosensitization/potentiation |
| Content Type | Text |
| Resource Type | Article |
