Synaptic plasticity rules with physiological calcium levels

Yanis Inglebert (1) , Johnatan Aljadeff (2) , Nicolas Brunel (2) , Dominique Debanne (1)

1 UNIS - Inserm U1072 - Unité de Neurobiologie des canaux Ioniques et de la Synapse
2 University of Chicago

Spike-timing-dependent plasticity (STDP) is considered as a primary mechanism underlying formation of new memories during learning. Despite the growing interest in activity-dependent plasticity, it is still unclear whether synaptic plasticity rules inferred from in vitro experiments are correct in physiological conditions. The abnormally high calcium concentration used in in vitro studies of STDP suggests that in vivo plasticity rules may differ significantly from in vitro experiments, especially since STDP depends strongly on calcium for induction. We therefore studied here the influence of extracellular calcium on synaptic plasticity. Using a combination of experimental (patch-clamp recording and Ca2+ imaging at CA3-CA1 synapses) and theoretical approaches, we show here that the classic STDP rule in which pairs of single pre-and postsynaptic action potentials induce synaptic modifications is not valid in the physiological Ca2+ range. Rather, we found that these pairs of single stimuli are unable to induce any synaptic modification in 1.3 and 1.5 mM calcium and lead to depression in 1.8 mM. Plasticity can only be recovered when bursts of postsynaptic spikes are used, or when neurons fire at sufficiently high frequency. In conclusion, the STDP rule is profoundly altered in physiological Ca2+, but specific activity regimes restore a classical STDP profile. STDP | hippocampus | computational model | plasticity Significance Spike-timing-dependent plasticity (STDP) is a form of synaptic modification thought to be a primary mechanism underlying formation of new memories. Despite triggering tremendous interest since its discovery, it is still unclear whether plasticity rules inferred from in vitro experiments are correct in physiological conditions. While STDP induction depends on intracellular calcium influx, all previous studies used an abnormally high concentration of extracellular calcium. Here, we study the influence of extracellular calcium on synaptic plasticity. We show that pairing single pre-and postsynaptic action potentials at hippocampal synapses does not induce plasticity in the physiological range of extracellular calcium. Rather, synaptic plasticity is induced only when bursts of postsynaptic spikes are used or when neurons fire at sufficiently high frequency.

Mots clés: Spike timing-dependent plasticity

Domaines: Neurobiologie

Yanis Inglebert, Johnatan Aljadeff, Nicolas Brunel, Dominique Debanne. Synaptic plasticity rules with physiological calcium levels. Proceedings of the National Academy of Sciences of the United States of America, 2020, 117 (52), pp.33639-33648. ⟨10.1073/pnas.2013663117⟩. ⟨hal-03138989⟩