Bidirectional synaptic plasticity rapidly modifies hippocampal representations

Abstract

15According to standard models of synaptic plasticity, correlated activity between 16 connected neurons drives changes in synaptic strengths to store associative 17 memories. Here we tested this hypothesis in vivo by manipulating the activity of 18 hippocampal place cells and measuring the resulting changes in spatial selectivity. 19 We found that the spatial tuning of place cells was rapidly reshaped via 20 bidirectional synaptic plasticity. To account for the magnitude and direction of 21 plasticity, we evaluated two models -a standard model that depended on 22 synchronous pre-and post-synaptic activity, and an alternative model that 23 1 depended instead on whether active synaptic inputs had previously been 1 potentiated. While both models accounted equally well for the data, they predicted 2 opposite outcomes of a perturbation experiment, which ruled out the standard 3 correlation-dependent model. Finally, network modeling suggested that this form 4 of bidirectional synaptic plasticity enables population activity, rather than pairwise 5 neuronal correlations, to drive plasticity in response to changes in the 6 environment. 7 8 Main Text 9 Activity-dependent changes in synaptic strength can flexibly alter the selectivity of 10 neuronal firing for particular features of the environment, providing a cellular substrate for 11 learning and memory. Various forms of Hebbian synaptic plasticity have been considered 12 for decades to be the main or even only synaptic plasticity mechanisms present within 13 most brain regions of a number of species. The core feature of such plasticity 14mechanisms is that they are autonomously driven by the repeated presence of correlated 15 presynaptic and postsynaptic activity that leads to either increases or decreases in 16 synaptic strength depending on the exact temporal coincidence (1-4). 17 The hippocampus plays an important role in many forms of learning and memory, 18 and the spatial firing rates of hippocampal place cells have been shown to change with 19 alterations in environmental context or the locations of salient features, like reward (5-20 11). Furthermore in CA1 neurons, place cell activity can emerge in a single trial following 21 a dendritic calcium spike (also called a plateau potential) (12-14). The form of synaptic 22 plasticity responsible for this rapid change in selectivity, termed behavioral timescale 23 2 synaptic plasticity (BTSP), modifies synaptic inputs active within a multi-second time 1 window around the plateau potential. That BTSP strengthens many synaptic inputs whose 2 activation did not cause or even coincide with postsynaptic activity suggests that it might 3 be a fundamentally different form of plasticity than classical correlation-driven Hebbian 4 plasticity (1-3). Such a plasticity rule could enable representation learning in cortical brain 5 regions like the hippocampus to be guided by delayed behavioral outcomes, rather than 6 by short timescale associations of neuronal input and output. However, it was not clear 7 from previous experiments...

Behavioral Time Scale Plasticity of Place Fields: Mathematical Analysis

“…These protocols have shown both an increase and a decrease in synaptic efficacies occurring in synapses that were active seconds before or after the plateau potentials. This plasticity, coined "behavioral time synaptic plasticity" (BTSP), is therefore also likely to depend on synaptic eligibility traces, both for LTP and LTD. A recent paper has shown that these traces likely depend only on presynaptic activity and the existing synaptic efficacy, and that change in synaptic efficacies depends on the overlap between these traces and an instructive signal that is activated by the plateau potential [18]. The data therefore supports a two-factor model in which the two factors are presynaptic activity and an instructive signal.…”

“…Experimental results in CA1 using both in vivo and slice preparations strongly suggest that presynaptic activity generates synaptic eligibility traces for both LTP and LTD [17,19]. Prior modeling work [18] shows, using simulations, that these two opposing traces, combined with a weight dependence can account for the place field plasticity observed in vivo.…”

“…The general framework for the model is as follows, emulating the setup for recent experiments in hippocampus [17,18]. A mouse runs along a treadmill of length L at velocity v. Experimenters record from a postsynaptic CA1 place cell which receives inputs from N presynaptic CA3 inputs.…”

“…The CA1 output has a ramp potential (i.e. the membrane potential relative to rest, low-pass filtered to eliminate spikes, see [18]) determined by the sum of its synaptic input:…”

“…Recent plasticity experiments in hippocampus in vivo [17,18] have shown placefield plasticity that occurs rapidly in response to either naturally occurring or artificially induced dendritic calcium spikes, also known as "plateau potentials". These protocols have shown both an increase and a decrease in synaptic efficacies occurring in synapses that were active seconds before or after the plateau potentials.…”