The transcription factor MEF2 directs developmental visually driven functional and structural metaplasticity.

TitleThe transcription factor MEF2 directs developmental visually driven functional and structural metaplasticity.
Publication TypeJournal Article
Year of Publication2012
AuthorsChen SXuan, Cherry A, Tari PKarimi, Podgorski K, Kwong YKay Kali, Haas K
JournalCell
Volume151
Issue1
Pagination41-55
Date Published2012 Sep 28
ISSN1097-4172
KeywordsAnimals, Auditory Perception, Brain, Caspases, MEF2 Transcription Factors, Myogenic Regulatory Factors, Neuronal Plasticity, Neurons, Receptors, N-Methyl-D-Aspartate, Sound, Transcription Factors, Visual Perception, Xenopus laevis, Xenopus Proteins
Abstract

Natural sensory input shapes both structure and function of developing neurons, but how early experience-driven morphological and physiological plasticity are interrelated remains unclear. Using rapid time-lapse two-photon calcium imaging of network activity and single-neuron growth within the unanesthetized developing brain, we demonstrate that visual stimulation induces coordinated changes to neuronal responses and dendritogenesis. Further, we identify the transcription factor MEF2A/2D as a major regulator of neuronal response to plasticity-inducing stimuli directing both structural and functional changes. Unpatterned sensory stimuli that change plasticity thresholds induce rapid degradation of MEF2A/2D through a classical apoptotic pathway requiring NMDA receptors and caspases-9 and -3/7. Knockdown of MEF2A/2D alone is sufficient to induce a metaplastic shift in threshold of both functional and morphological plasticity. These findings demonstrate how sensory experience acting through altered levels of the transcription factor MEF2 fine-tunes the plasticity thresholds of brain neurons during neural circuit formation.

URLhttps://www.ncbi.nlm.nih.gov/pubmed/23021214
DOI10.1016/j.cell.2012.08.028
Alternate JournalCell
PubMed ID23021214
Grant List / / Canadian Institutes of Health Research / Canada