The Transcription Factor MEF2 Directs Developmental Visually Driven Functional and Structural Metaplasticity
- Resource Type
- Authors
- Angus Cherry; Parisa Karimi Tari; Simon X Chen; Kaspar Podgorski; Kurt Haas; Yue Kay Kali Kwong
- Source
- Cell. (1):41-55
- Subject
- Mef2
Regulator
Stimulation
Sensory system
Xenopus Proteins
Biology
Receptors, N-Methyl-D-Aspartate
General Biochemistry, Genetics and Molecular Biology
Xenopus laevis
03 medical and health sciences
0302 clinical medicine
Calcium imaging
Metaplasticity
Animals
Transcription factor
030304 developmental biology
Neurons
0303 health sciences
Neuronal Plasticity
MEF2 Transcription Factors
Biochemistry, Genetics and Molecular Biology(all)
Brain
Anatomy
Sound
Myogenic Regulatory Factors
Caspases
Auditory Perception
Visual Perception
NMDA receptor
Neuroscience
030217 neurology & neurosurgery
Transcription Factors
- Language
- English
- ISSN
- 0092-8674
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.