Spontaneous Activity Drives Local Synaptic Plasticity In Vivo

TY - JOUR

T1 - Spontaneous Activity Drives Local Synaptic Plasticity In Vivo

AU - Winnubst, Johan

AU - Cheyne, Juliette E

AU - Niculescu, Dragos

AU - Lohmann, C.

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/7/15

Y1 - 2015/7/15

N2 - 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 μm) 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. VIDEO ABSTRACT.

AB - 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 μm) 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. VIDEO ABSTRACT.

U2 - 10.1016/j.neuron.2015.06.029

DO - 10.1016/j.neuron.2015.06.029

M3 - Article

C2 - 26182421

SN - 0896-6273

VL - 87

SP - 399

EP - 410

JO - Neuron

JF - Neuron

IS - 2

ER -