Endocannabinoid dynamics gate spike-timing dependent depression and potentiation (Cui et al 2016)


The endocannabinoid (eCB) system is considered involved in synaptic depression. Recent reports have also linked eCBs to synaptic potentiation. However it is not known how eCB signaling may support such bidirectionality. To question the mechanisms of this phenomena in spike-timing dependent plasticity (STDP) at corticostriatal synapses, we combined electrophysiology experiments with biophysical modeling. We demonstrate that STDP 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). Therefore, just like neurotransmitters glutamate or GABA, eCB form a bidirectional system.

Model Type: Synapse; Channel/Receptor

Cell Type(s): Neostriatum medium spiny direct pathway GABA cell; Neostriatum medium spiny indirect pathway GABA cell; Neostriatum spiny neuron

Currents: I L high threshold; I Calcium; I_SERCA; I Cl, leak; Ca pump

Receptors: AMPA; NMDA; mGluR; Glutamate; IP3

Model Concept(s): Ion Channel Kinetics; Coincidence Detection; Parameter Fitting; Synaptic Plasticity; Long-term Synaptic Plasticity; Signaling pathways; STDP; Calcium dynamics; Parameter sensitivity; G-protein coupled; Neuromodulation

Simulation Environment: FORTRAN; Python

References:

Cui Y, Prokin I, Xu H, Delord B, Genet S, Venance L, Berry H. (2016). Endocannabinoid dynamics gate spike-timing dependent depression and potentiation. Elife 5 [PubMed]