Nature Neuroscience 9, 887 - 895 (2006)
Published online: 28 May 2006; | doi:10.1038/nn1708
AMPA receptors regulate transcription of the plasticity-related immediate-early gene ArcVikram R Rao1, 3, 4, Sean A Pintchovski1, 2, Jeannie Chin1, 5, Carol L Peebles1, 2, 4, Siddhartha Mitra1, 3, 4
& Steven Finkbeiner1, 2, 3, 4, 5, 61
Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA. 2
Neuroscience Graduate Program, University of California, San Francisco, California 94158, USA. 3
Biomedical Sciences Graduate Program, University of California, San Francisco, California 94158, USA. 4
Medical Scientist Training Program, University of California, San Francisco, California 94158, USA. 5
Department of Neurology, University of California, San Francisco, California 94158, USA. 6
Department of Physiology, University of California, San Francisco, California 94158, USA.
Correspondence should be addressed to Steven Finkbeiner sfinkbeiner@gladstone.ucsf.edu 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.
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