Location-dependent synaptic plasticity rules by dendritic spine cooperativity

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.

Increased Prevalence of Calcium Transients across the Dendritic Arbor during Place Field Formation

“…We identified 4 putative local dendritic spikes from 3 different branches that closely resembled those observed in slice (Figure S3C, D). The total length of dendrite invaded by these transients could be measured since they were contained within the imaged branch: range of 5.9 – 8.5 um, mean of 7.5 um, similar to other reports (Brandalise et al, 2016; Lavzin et al, 2012; Major et al, 2008; Palmer et al, 2014; Schiller et al, 2000; Weber et al, 2016). We first assumed that the spread of these 4 putative local dendritic spikes represents an estimate of the spread of the 30 putative local dendritic spikes observed during the delay period (the two classes of putative spikes, 4 and 30, had similar amplitude and kinetics as well).…”

“…If synaptic plasticity is occurring during this delay period to contribute to the formation of new place fields, it appears to occur in the absence of somatic action potential firing and back-propagation into the dendrites. We therefore looked for dendrite-localized calcium transients that might result from local clustered synaptic input (possibly generating local regenerative events) capable of inducing synaptic potentiation in the absence of somatic firing (Brandalise et al, 2016; Losonczy and Magee, 2006; Major et al, 2008; Milojkovic et al, 2007; Oakley et al, 2001; Palmer et al, 2014; Schiller et al, 2000; Weber et al, 2016; Wei et al, 2001). …”

“…We used established glutamate uncaging techniques to mimic synaptic inputs at selected spines along a single basal dendrite of a CA1 neuron expressing GCaMP6f (Bloodgood and Sabatini, 2007; Losonczy and Magee, 2006; Losonczy et al, 2008). Using a 2-photon microscope to image dendrites during spine stimulation, we found that simultaneous (within 5 ms) clustered input within 5–15 μm onto multiple spines (3 or more) often generated dendritic calcium transients that spread beyond the stimulated spines and into the nearby shaft (Figure S3D), a signature suggesting local dendritic spike generation (Brandalise et al, 2016; Losonczy and Magee, 2006; Major et al, 2008; Milojkovic et al, 2007; Oakley et al, 2001; Palmer et al, 2014; Schiller et al, 2000; Weber et al, 2016; Wei et al, 2001). These dendrite-localized calcium transients stimulated in slice had transient amplitudes and durations similar to the dendrite-localized transients recorded during the delay period of delayed onset place fields in behaving mice (Figure S3).…”

“…Have amplitudes and durations similar to transients stimulated with clustered synaptic input in slice, we conclude that these dendrite-localized calcium transients are caused by clustered input onto single basal branches, presumably generating local dendritic spikes, during the delay period in delayed onset place cells. Some of these 30 dendrite-localized calcium transients may represent nonlinear amplification of spine calcium signals by clustered synaptic input that does not reach full dendritic spike status (Weber et al, 2016), and therefore we refer to these 30 events as “putative” local dendritic spikes. Importantly, both full dendritic spikes and clustered inputs that just fall short of generating local dendritic spikes are capable of triggering synaptic potentiation (Weber et al, 2016).…”

“…Some of these 30 dendrite-localized calcium transients may represent nonlinear amplification of spine calcium signals by clustered synaptic input that does not reach full dendritic spike status (Weber et al, 2016), and therefore we refer to these 30 events as “putative” local dendritic spikes. Importantly, both full dendritic spikes and clustered inputs that just fall short of generating local dendritic spikes are capable of triggering synaptic potentiation (Weber et al, 2016). …”