Extracellular Signal-Regulated Protein Kinase Activation Is Required for Metabotropic Glutamate Receptor-Dependent Long-Term Depression in Hippocampal Area CA1
| Autor: | Kimberly M. Huber, Christine A. Daly, Sean M. Gallagher, Mark F. Bear |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
MAPK/ERK pathway
Glycine In Vitro Techniques Mitogen-activated protein kinase kinase Receptors Metabotropic Glutamate Hippocampus p38 Mitogen-Activated Protein Kinases Dihydroxyphenylglycine chemistry.chemical_compound mental disorders Excitatory Amino Acid Agonists Animals Rats Long-Evans ASK1 Enzyme Inhibitors Phosphorylation Long-term depression Dose-Response Relationship Drug MAP kinase kinase kinase Long-Term Synaptic Depression musculoskeletal neural and ocular physiology General Neuroscience Metabotropic glutamate receptor 7 Resorcinols Rats Cell biology Enzyme Activation nervous system chemistry Metabotropic glutamate receptor Mitogen-Activated Protein Kinases Brief Communications Signal Transduction |
| Zdroj: | The Journal of Neuroscience. 24:4859-4864 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.5407-03.2004 |
| Popis: | Activation of group 1 metabotropic glutamate receptors (mGluRs) induces long-term depression (LTD) of synaptic transmission that relies on dendritic protein synthesis. We investigated the signal transduction pathways required for mGluR-LTD to identify candidate mechanisms for mGluR regulation of synaptic protein synthesis. Our results demonstrate a role for extracellular signal-regulated protein kinase (ERK), a subclass of the mitogen-activated protein kinases (MAPKs), in mGluR-LTD in area CA1 of the rat hippocampus. Inhibitors of the upstream kinase of ERK, MAP/ERK kinase significantly reduce mGluR-LTD induced by the group 1 agonist dihydroxyphenylglycine (DHPG) and synaptic stimulation but do not affect NMDA receptor-dependent LTD. In contrast, inhibitors of p38 MAPK were ineffective against DHPG-induced LTD. Consistent with the role of ERK in mGluR-LTD, we observed that DHPG treatment of hippocampal slices (isolated CA1), at concentrations that induce LTD, results in a robust phosphorylation of ERK but not of p38 MAPK. These results point to ERK as an important regulator of mGluR-LTD and a potential mechanism for mGluR regulation of synaptic protein synthesis. |
| Databáze: | OpenAIRE |
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