AMPA receptors regulate transcription of the plasticity-related immediate-early gene Arc
| Autor: | Vikram R. Rao, Jeannie Chin, Steven Finkbeiner, Carol L. Peebles, Siddhartha Mitra, Sean A Pintchovski |
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| Rok vydání: | 2006 |
| Předmět: |
Blotting
Western Gene Expression Nonsynaptic plasticity Nerve Tissue Proteins AMPA receptor In Vitro Techniques Biology Bicuculline Transfection GABA Antagonists Metaplasticity Animals Drug Interactions Receptors AMPA Enzyme Inhibitors Long-term depression Cells Cultured In Situ Hybridization Cerebral Cortex Neurons Brain-derived neurotrophic factor Neuronal Plasticity Synaptic scaling Brain-Derived Neurotrophic Factor General Neuroscience Blotting Northern Immunohistochemistry Rats Cytoskeletal Proteins Animals Newborn nervous system Synaptic plasticity Calcium Excitatory Amino Acid Antagonists Neuroscience Ion channel linked receptors |
| Zdroj: | Nature Neuroscience. 9:887-895 |
| ISSN: | 1546-1726 1097-6256 |
| Popis: | Learning and memory depend critically on long-term synaptic plasticity, which requires neuronal gene expression. In the prevailing view, AMPA receptors mediate fast excitatory synaptic transmission and effect short-term plasticity, but they do not directly regulate neuronal gene expression. By studying regulation of Arc, a gene required for long-term plasticity, we uncovered a new role for AMPA receptors in neuronal gene expression. Spontaneous synaptic activity or activity induced by brain-derived neurotrophic factor (BDNF) elicited Arc expression in cultures of rat cortical neurons and in organotypic brain slices. Notably, inhibiting AMPA receptors strongly potentiated activity-dependent Arc expression. We found that AMPA receptors negatively regulate Arc transcription, but not translation or stability, through a mechanism involving a pertussis toxin-sensitive G protein. These results provide insights into the activity-dependent mechanisms of Arc expression and suggest that, in addition to effecting short-term plasticity, AMPA receptors regulate genes involved in long-term plasticity. |
| Databáze: | OpenAIRE |
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