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Cell ; 151(1): 41-55, 2012 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-23021214

RESUMO

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.


Assuntos
Encéfalo/embriologia , Fatores de Regulação Miogênica/metabolismo , Plasticidade Neuronal , Fatores de Transcrição/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus laevis/embriologia , Animais , Percepção Auditiva , Encéfalo/citologia , Caspases/metabolismo , Fatores de Transcrição MEF2 , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Som , Percepção Visual
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