title: The transcription factor MEF2 directs developmental visually driven functional and structural metaplasticity.
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.
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: Simon Xuan
authors.initials: SX
authors.lastname: Chen
authors.forename: Angus
authors.initials: A
authors.lastname: Cherry
authors.forename: Parisa Karimi
authors.initials: PK
authors.lastname: Tari
authors.forename: Kaspar
authors.initials: K
authors.lastname: Podgorski
authors.forename: Yue Kay Kali
authors.initials: YK
authors.lastname: Kwong
authors.forename: Kurt
authors.initials: K
authors.lastname: Haas
mesh_terms: D000818:Animals; D001307:Auditory Perception; D001921:Brain / Q000166:cytology / Q000196:embryology*; D020169:Caspases / Q000378:metabolism; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013016:Sound; D014157:Transcription Factors / Q000378:metabolism*; D014796:Visual Perception; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology*
chemical_list: D064326:MEF2 Transcription Factors; C578034:MEF2 protein, Xenopus; D018006:Myogenic Regulatory Factors; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; D029867:Xenopus Proteins; D020169:Caspases