Journal
NEURON
Volume 87, Issue 2, Pages 399-410Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2015.06.029
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Funding
- Netherlands Organization for Scientific Research (NWO, TOP ZonMw) [912.10.009]
- Netherlands Organization for Scientific Research (NWO, ALW Open Program) [819.02.017, 822.02.006]
- Netherlands Organization for Scientific Research (NWO, Vici) [865.12.001]
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Spontaneous activity fine-tunes neuronal connections in the developing brain. To explore the underlying synaptic plasticity mechanisms, we monitored naturally occurring changes in spontaneous activity at individual synapses with whole-cell patch-clamp recordings and simultaneous calcium imaging in the mouse visual cortex in vivo. Analyzing activity changes across large populations of synapses revealed a simple and efficient local plasticity rule: synapses that exhibit low synchronicity with nearby neighbors (<12 mu m) become depressed in their transmission frequency. Asynchronous electrical stimulation of individual synapses in hippocampal slices showed that this is due to a decrease in synaptic transmission efficiency. Accordingly, experimentally increasing local synchronicity, by stimulating synapses in response to spontaneous activity at neighboring synapses, stabilized synaptic transmission. Finally, blockade of the high-affinity proBDNF receptor p75(NTR) prevented the depression of asynchronously stimulated synapses. Thus, spontaneous activity drives local synaptic plasticity at individual synapses in an out-of-sync, lose-your-link fashion through proBDNF/p75(NTR) signaling to refine neuronal connectivity.
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