Abstract

In Hebbian plasticity, neural circuits adjust their synaptic weights depending on patterned firing. Spike-timing-dependent plasticity (STDP), a synaptic Hebbian learning rule, relies on the order and timing of the paired activities in pre- and postsynaptic neurons. Classically, in ex vivo experiments, STDP is assessed with deterministic (constant) spike timings and time intervals between successive pairings, thus exhibiting a regularity that differs from biological variability. Hence, STDP emergence from noisy inputs as occurring in in vivo-like firing remains unresolved. Here, we used noisy STDP pairings where the spike timing and/or interval between pairings were jittered. We explored with electrophysiology and mathematical modeling, the impact of jitter on three forms of STDP at corticostriatal synapses: NMDAR-LTP, endocannabinoid-LTD and endocannabinoid-LTP. We found that NMDAR-LTP was highly fragile to jitter, whereas endocannabinoid-plasticity appeared more resistant. When the frequency or number of pairings was increased, NMDAR-LTP became more robust and could be expressed despite strong jittering. Our results identify endocannabinoid-plasticity as a robust form of STDP, whereas the sensitivity to jitter of NMDAR-LTP varies with activity frequency. This provides new insights into the mechanisms at play during the different phases of learning and memory and the emergence of Hebbian plasticity in in vivo-like activity.

Highlights

  • In Hebbian plasticity, neural circuits adjust their synaptic weights depending on patterned firing

  • Inset: distribution of the 100 ΔtSTDP. (d2) Averaged time-courses of tLTD induced by 100 pre-post pairings; this tLTD was CB1R-mediated because prevented by AM251 (3 μM). (d3) Relationship between the Spiketiming-dependent plasticity (STDP) magnitude and the jitter. (e) Corticostriatal eCB-timing-dependent-long-term potentiation (tLTP) induced by 10 post-pre pairings with fixed ΔtSTDP. (e1) Example of tLTP induced by 10 post-pre pairings; the mean baseline EPSC amplitude, 147 ± 3 pA, increased by 43% to 209 ± 9 pA 45 minutes after pairings

  • Corticostriatal synapses exhibit a bidirectional STDP in which NMDAR-tLTP, eCB-tLTD29,32–34 or eCB-tLTP12,13 are induced depending on the number of pairings (Npairings) and the spike timing (ΔtSTDP)

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Summary

Introduction

In Hebbian plasticity, neural circuits adjust their synaptic weights depending on patterned firing. Our results identify endocannabinoid-plasticity as a robust form of STDP, whereas the sensitivity to jitter of NMDAR-LTP varies with activity frequency. This provides new insights into the mechanisms at play during the different phases of learning and memory and the emergence of Hebbian plasticity in in vivo-like activity. A typical experimental protocol consists in pairing pre- and postsynaptic stimulations with a fixed ΔtSTDP (ranging from −30 to +30 ms for plasticity induction); ΔtSTDP < 0 when the postsynaptic stimulation occurs before the paired presynaptic one (post-pre pairings), whereas ΔtSTDP > 0 when the presynaptic stimulation occurs before the postsynaptic one (pre-post pairings) These pairings are repeated between 15 and 200 times (between 0.1 and 5 Hz) with the spike timing and the time interval between successive pairings being kept constant. Inset: distribution of the 10 ΔtSTDP. (e2) Averaged time-courses of tLTP induced by 10 post-pre pairings; this tLTP was CB1R-mediated because prevented by AM251. (e3) Relationship between the STDP magnitude and the jitter. (c1-d1-e1) Insets: average of 12 successive EPSC amplitude at baseline (black traces) and at 40–50 min after pairings (grey traces)

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