MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function


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Barbosa A. C. , Kim M., Ertunc M. , Adachi M., Nelson E. D. , McAnally J., ...More

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol.105, no.27, pp.9391-9396, 2008 (Journal Indexed in SCI) identifier

  • Publication Type: Article / Article
  • Volume: 105 Issue: 27
  • Publication Date: 2008
  • Doi Number: 10.1073/pnas.0802679105
  • Title of Journal : PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Page Numbers: pp.9391-9396
  • Keywords: synaptic transmission, synaptogenesis, learning deficits, ACTIVITY-DEPENDENT REGULATION, TRANSGENIC MICE, NERVOUS-SYSTEM, RADIAL GLIA, PLASTICITY, HIPPOCAMPUS, DIFFERENTIATION, EXPRESSION, CREB, MORPHOGENESIS

Abstract

Learning and memory depend on the activity-dependent structural plasticity of synapses and changes in neuronal gene expression. We show that deletion of the MEF2C transcription factor in the CNS of mice impairs hippocampal-dependent learning and memory. Unexpectedly, these behavioral changes were accompanied by a marked increase in the number of excitatory synapses and potentiation of basal and evoked synaptic transmission. Conversely, neuronal expression of a superactivating form of MEF2C results in a reduction of excitatory postsynaptic sites without affecting learning and memory performance. We conclude that MEF2C limits excessive synapse formation during activity-dependent refinement of synaptic connectivity and thus facilitates hippocampal-dependent learning and memory.