Endocannabinoid dynamics gate spike-timing dependent depression and potentiation
- College de France, France
- French Institute for Research in Computer Science and Automation, France
- University Pierre et Marie Curie, France
Abstract
Synaptic plasticity is a cardinal cellular mechanism for learning and memory. The endocannabinoid (eCB) system has emerged as a pivotal pathway for synaptic plasticity because of its widely characterized ability to depress synaptic transmission on short- and long-term scales. Recent reports indicate that eCBs also mediate potentiation of the synapse. However it is not known how eCB signaling may support bidirectionality. Here, we combined electrophysiology experiments with mathematical modeling to question the mechanisms of eCB bidirectionality in spike-timing dependent plasticity (STDP) at corticostriatal synapses. We demonstrate that STDP outcome is controlled by eCB levels and dynamics: prolonged and moderate levels of eCB lead to eCB-mediated long-term depression (eCB-tLTD) while short and large eCB transients produce eCB-mediated long-term potentiation (eCB-tLTP). Moreover, we show that eCB-tLTD requires active calcineurin whereas eCB-tLTP necessitates the activity of presynaptic PKA. Therefore, just like glutamate or GABA, eCB form a bidirectional system to encode learning and memory.
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Animal experimentation: All experiments were performed in accordance with local animal welfare committee (Center for Interdisciplinary Research in Biology and EU guidelines, directive 2010/63/EU).
Copyright
© 2016, Cui et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Endocannabinoid dynamics gate spike-timing dependent depression and potentiation
eLife 5:e13185.
https://doi.org/10.7554/eLife.13185
