Rates of synapse formation and elimination change over the course of postnatal development, but little is known of molecular mechanisms that mediate this developmental switch. Here, we report that the dendritic RNA-binding protein fragile X mental retardation protein (FMRP) bidirectionally and cell autonomously regulates excitatory synaptic function, which depends on developmental age as well as function of the activity-dependent transcription factor myocyte enhancer factor 2 (MEF2). The acute postsynaptic expression of FMRP in CA1 neurons of hippocampal slice cultures (during the first postnatal week, P6-P7) promotes synapse function and maturation. In contrast, the acute expression of FMRP or endogenous FMRP in more mature neurons (during the second postnatal week; P13-P16) suppresses synapse number. The ability of neuronal depolarization to stimulate MEF2 transcriptional activity increases over this same developmental period. Knockout of endogenous MEF2 isoforms causes acute postsynaptic FMRP expression to promote, instead of eliminate, synapses onto 2-week-old neurons. Conversely, the expression of active MEF2 in neonatal neurons results in a precocious FMRP-dependent synapse elimination. Our findings suggest that FMRP and MEF2 function together to fine tune synapse formation and elimination rates in response to neuronal activity levels over the course of postnatal development.
Pubmed ID: 23511190 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Commercial organism provider selling mice, rats and other model animals. American corporation specializing in a variety of pre-clinical and clinical laboratory services for the pharmaceutical, medical device and biotechnology industries. It also supplies assorted biomedical products and research and development outsourcing services for use in the pharmaceutical industry. (Wikipedia)
View all literature mentionsA software application which allows reconstruction of neuronal structures from confocal and multi-photon images. NeuronStudio provides tools for manual, semi-manual, and automatic tracing of the dendritic arbor, as well as manual and automatic detection and classification of dendritic spines. Advanced 2D and 3D visualization techniques facilitate the verification of the reconstruction, as well as allowing accurate manual editing. The most current version is Version 0.9.92 which was last updated on November 19, 2009.
View all literature mentions