MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function.
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.
Barbosa
Ana C
AC
Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
Kim
Mi-Sung
MS
Ertunc
Mert
M
Adachi
Megumi
M
Nelson
Erika D
ED
McAnally
John
J
Richardson
James A
JA
Kavalali
Ege T
ET
Monteggia
Lisa M
LM
Bassel-Duby
Rhonda
R
Olson
Eric N
EN
D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism / Q000648:ultrastructure; D017353:Gene Deletion; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D017774:Long-Term Potentiation; D064326:MEF2 Transcription Factors; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D019580:Perforant Pathway / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission; D014157:Transcription Factors / Q000378:metabolism*
D017405:Herpes Simplex Virus Protein Vmw65; D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors