|Title||The transcription factor MEF2 directs developmental visually driven functional and structural metaplasticity.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Chen SXuan, Cherry A, Tari PKarimi, Podgorski K, Kwong YKay Kali, Haas K|
|Date Published||2012 Sep 28|
|Keywords||Animals, 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|
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.
|Grant List||/ / Canadian Institutes of Health Research / Canada|