کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2035747 | 1072218 | 2012 | 15 صفحه PDF | دانلود رایگان |
SummaryNatural 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.
Graphical AbstractFigure optionsDownload high-quality image (290 K)Download as PowerPoint slideHighlights
► The transcription factor MEF2 is a master regulator of developmental metaplasticity
► Developmental structural and functional neuronal plasticity are coordinated
► Unpatterned visual stimuli induce loss of MEF2 via NMDARs and caspases-9, -3/7
► Knockdown of MEF2 is sufficient to induce a metaplastic shift in plasticity responses
Journal: - Volume 151, Issue 1, 28 September 2012, Pages 41–55