Roles for the MEF2 Transcription Factors in Synapse and Circuit Development and Plasticity

Development and refinement of mammalian synaptic connections occurs during the postnatal period and relies on sensory experience and neuronal activity. Accumulating evidence supports a role for experience and activity-regulated transcriptional control in formation and refinement of synapses and circuits during development. Here we review evidence for roles of the myocyte enhancer factor 2 (MEF2A-D) family of transcription factors in postnatal synapse and circuit development. The MEF2A/C/D transcription factors have been primarily implicated in activity-dependent refinement or elimination of excitatory synaptic connections in the hippocampus and cerebellum. More recent work has revealed roles for MEF2C in experience-dependent and input-specific regulation of excitatory synapses in the cortex, uncovering novel mechanisms of postnatal circuit development. MEF2 transcription factors function as sensors of neuronal activity induced by diverse stimuli, such as sensory experience, sleep, drugs of abuse and learning and serve to refine synaptic connectivity and function in response to these experiences. Loss of function of MEF2C is associated with neurodevelopmental disorders such as schizophrenia and autism. Conversely, transcriptional activities of MEF2A and MEF2C are positively associated with cognitive performance in both mice and humans. We propose it is the ability of MEF2 to refine synaptic connectivity in response to experience that promotes cognition.