Location-dependent synaptic plasticity rules by dendritic spine cooperativity.

Jens P Weber,Ádám Magó,Balázs B Ujfalussy,Marina Polito,Bertalan K Andrásfalvy,Judit K Makara

doi:10.1038/ncomms11380

Abstract

Nonlinear interactions between coactive synapses enable neurons to discriminate between spatiotemporal patterns of inputs. Using patterned postsynaptic stimulation by two-photon glutamate uncaging, here we investigate the sensitivity of synaptic Ca2+ signalling and long-term plasticity in individual spines to coincident activity of nearby synapses. We find a proximodistally increasing gradient of nonlinear NMDA receptor (NMDAR)-mediated amplification of spine Ca2+ signals by a few neighbouring coactive synapses along individual perisomatic dendrites. This synaptic cooperativity does not require dendritic spikes, but is correlated with dendritic Na+ spike propagation strength. Furthermore, we show that repetitive synchronous subthreshold activation of small spine clusters produces input specific, NMDAR-dependent cooperative long-term potentiation at distal but not proximal dendritic locations. The sensitive synaptic cooperativity at distal dendritic compartments shown here may promote the formation of functional synaptic clusters, which in turn can facilitate active dendritic processing and storage of information encoded in spatiotemporal synaptic activity patterns.

Highlights

Nonlinear interactions between coactive synapses enable neurons to discriminate between spatiotemporal patterns of inputs
It is well documented that extensive synaptic activation in a dendritic region of hippocampal and neocortical pyramidal cells (PCs) can reach the threshold of regenerative local dendritic spikes mediated by voltage-gated Na þ or Ca2 þ channels (VGNCs, VGCCs), or NMDA receptor (NMDAR), depending on the dendritic region[31]
We found that the threshold for spine Ca2 þ supralinearity by spatiotemporally clustered synapses (1) is lower than that of voltage response supralinearities, (2) depends on dendritic location of the cluster with a decreasing proximodistal gradient and (3) is coregulated with dendritic Na þ spike propagation strength

Summary

Introduction

Nonlinear interactions between coactive synapses enable neurons to discriminate between spatiotemporal patterns of inputs. It is well documented that extensive synaptic activation in a dendritic region of hippocampal and neocortical PCs can reach the threshold of regenerative local dendritic spikes mediated by voltage-gated Na þ or Ca2 þ channels (VGNCs, VGCCs), or NMDARs, depending on the dendritic region[31] These events attracted much interest for providing supralinear dendritic signals influencing somatic action potential (AP) output and inducing synaptic plasticity[11,33,34,35,36]. In most studies demonstrating the spatial clustering of functionally related synapses, the clusters were surprisingly small and tight, consisting of only a few synapses (approximately two to six) located on short dendritic segments (B5–15 mm)[2,3,4,7,8,9] Sporadic activation of such small clusters likely produces depolarization in the voltage range subthreshold for dendritic spikes, where EPSPs sum roughly linearly[20,22,37]. It may logically follow that location dependency may extend to subthreshold cooperative synaptic interactions[17] and perhaps to plasticity, but this hypothesis has not yet been tested experimentally

Methods

Results

Conclusion