NMDA receptors inhibit synapse unsilencing during brain development Export

@article{sungmo jc, abstract = {How the billions of synapses in the adult mammalian brain are precisely specified remains one of the fundamental questions of neuroscience. Although a genetic program is likely to encode the basic neural blueprint, much evidence suggests that experience-driven activity through NMDA receptors wires up neuronal circuits by inducing a process similar to long-term potentiation. To test this notion directly, we eliminated NMDA receptors before and during synaptogenesis in single cells in vitro and in vivo. Although the prevailing model would predict that NMDA receptor deletion should strongly inhibit the maturation of excitatory circuits, we find that genetic ablation of NMDA receptor function profoundly increases the number of functional synapses between neurons. Conversely, reintroduction of NMDA receptors into NR1-deficient neurons reduces the number of functional inputs, a process requiring network activity and NMDA receptor function. Although NMDA receptor deletion increases the strength of unitary connections, it does not alter neuronal morphology, suggesting that basal NMDA receptor activation blocks the recruitment of AMPA receptors to silent synapses. Based on these results we suggest a new model for the maturation of excitatory synapses in which ongoing activation of NMDA receptors prevents premature synaptic maturation by ensuring that only punctuated bursts of activity lead to the induction of a functional synapse for the activity-dependent wiring of neural circuitry. 10.1073/pnas.0800946105}, author = {Adesnik, Hillel and Li, Guangnan and During, Matthew J. and Pleasure, Samuel J. and Nicoll, Roger A.}, citeulike-article-id = {2687992}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0800946105}, citeulike-linkout-1 = {http://www.pnas.org/cgi/content/abstract/105/14/5597}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18375768}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18375768}, day = {8}, doi = {10.1073/pnas.0800946105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {080724, jc, sungmo}, month = {April}, number = {14}, pages = {5597--5602}, posted-at = {2008-07-20 07:11:19}, priority = {2}, title = {NMDA receptors inhibit synapse unsilencing during brain development}, url = {http://dx.doi.org/10.1073/pnas.0800946105}, volume = {105}, year = {2008} }

TY - JOUR ID - sungmo jc L3 - citeulike-article-id:2687992 N2 - How the billions of synapses in the adult mammalian brain are precisely specified remains one of the fundamental questions of neuroscience. Although a genetic program is likely to encode the basic neural blueprint, much evidence suggests that experience-driven activity through NMDA receptors wires up neuronal circuits by inducing a process similar to long-term potentiation. To test this notion directly, we eliminated NMDA receptors before and during synaptogenesis in single cells in vitro and in vivo. Although the prevailing model would predict that NMDA receptor deletion should strongly inhibit the maturation of excitatory circuits, we find that genetic ablation of NMDA receptor function profoundly increases the number of functional synapses between neurons. Conversely, reintroduction of NMDA receptors into NR1-deficient neurons reduces the number of functional inputs, a process requiring network activity and NMDA receptor function. Although NMDA receptor deletion increases the strength of unitary connections, it does not alter neuronal morphology, suggesting that basal NMDA receptor activation blocks the recruitment of AMPA receptors to silent synapses. Based on these results we suggest a new model for the maturation of excitatory synapses in which ongoing activation of NMDA receptors prevents premature synaptic maturation by ensuring that only punctuated bursts of activity lead to the induction of a functional synapse for the activity-dependent wiring of neural circuitry. 10.1073/pnas.0800946105 IS - 14 JF - Proceedings of the National Academy of Sciences EP - 5602 TI - NMDA receptors inhibit synapse unsilencing during brain development VL - 105 SP - 5597 KW - 080724 KW - jc KW - sungmo AU - Adesnik, Hillel AU - Li, Guangnan AU - During, Matthew AU - Pleasure, Samuel AU - Nicoll, Roger PY - 2008/04/08/ UR - http://dx.doi.org/10.1073/pnas.0800946105 ER -