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Endocannabinoid dynamics gate spike-timing dependent depression and potentiation.
Yihui Cui1,2, Ilya Prokin3,4, Hao Xu1,2
1Center for Interdisciplinary Research in Biology, College de France, INSERM U1050, CNRS UMR7241, Labex Memolife, Paris, France.
Elife
|February 28, 2016
Summary
The endocannabinoid system bidirectionally controls synaptic plasticity for learning and memory. Moderate, sustained endocannabinoid levels induce long-term depression, while brief, large transients cause long-term potentiation.
Area of Science:
- Neuroscience
- Cellular Biology
- Systems Biology
Background:
- Synaptic plasticity is crucial for learning and memory.
- The endocannabinoid (eCB) system modulates synaptic transmission.
- The mechanisms underlying eCB-mediated bidirectionality in plasticity remain unclear.
Purpose of the Study:
- To investigate the mechanisms of endocannabinoid bidirectionality in spike-timing dependent plasticity (STDP).
- To determine how eCB levels and dynamics influence synaptic plasticity outcomes at corticostriatal synapses.
Main Methods:
- Electrophysiology experiments
- Mathematical modeling
- Analysis of corticostriatal synapses
Main Results:
- STDP outcome is determined by eCB levels and dynamics.
- Prolonged, moderate eCB levels induce eCB-mediated long-term depression (eCB-tLTD).
- Short, large eCB transients induce eCB-mediated long-term potentiation (eCB-tLTP).
- eCB-tLTD requires calcineurin activity.
- eCB-tLTP requires presynaptic PKA activity.
Conclusions:
- The endocannabinoid system provides a bidirectional mechanism for encoding learning and memory.
- eCB signaling, similar to neurotransmitters like glutamate and GABA, exhibits bidirectionality.
- Distinct molecular pathways (calcineurin for LTD, PKA for LTP) underlie eCB-mediated synaptic plasticity.
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