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

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Accession:187605
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.
Reference:
1 . 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:e13185 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Synapse; Channel/Receptor;
Brain Region(s)/Organism:
Cell Type(s): Neostriatum medium spiny direct pathway GABA cell; Neostriatum medium spiny indirect pathway GABA cell; Neostriatum spiny neuron;
Channel(s): I L high threshold; I Calcium; I_SERCA; I Cl, leak; Ca pump;
Gap Junctions:
Receptor(s): AMPA; NMDA; mGluR; Glutamate; IP3;
Gene(s):
Transmitter(s):
Simulation Environment: FORTRAN; Python;
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;
Implementer(s):
Search NeuronDB for information about:  Neostriatum medium spiny direct pathway GABA cell; Neostriatum medium spiny indirect pathway GABA cell; AMPA; NMDA; mGluR; Glutamate; IP3; I L high threshold; I Calcium; I_SERCA; I Cl, leak; Ca pump;
!    -*- f95 -*-
! (c) 2016 - Ilya Prokin - isprokin@gmail.com - https://sites.google.com/site/ilyaprokin
! INRIA Rhone-Alpes
! STDP model : A simple three state kinetic model of activation of cannabinoid receptor type 1 (CB1R)
! by 2-arachidonoylglycerol (2-AG) and anandamide (AEA)
! The modeling approach is similar the one of Destexhe et al 1994.

module CB1R

    use pars_mod
    !use pars_CB1R_mod

    implicit none

    contains

    subroutine o_d_CB1R_IC_setup(eCB_bl, pars,  o_CB1R0, d_CB1R0)
        implicit none
        real*8, intent(in) :: eCB_bl
        type(pars_type), intent(in) :: pars
        real*8 :: gameps, Ab
        real*8, intent(out) :: o_CB1R0, d_CB1R0
        gameps=pars%CB1R%Gamma/pars%CB1R%Epsilon
        Ab=(pars%CB1R%Beta+pars%CB1R%Gamma)/pars%CB1R%Alpha
        o_CB1R0 = eCB_bl/(Ab+(1+gameps)*eCB_bl)
        d_CB1R0 = o_CB1R0*gameps
    end subroutine o_d_CB1R_IC_setup

    subroutine do_dd_CB1R(eCB,o_CB1R,d_CB1R,pars,  do_CB1R,dd_CB1R)
        implicit none
        real*8, intent(in) :: eCB,o_CB1R,d_CB1R
        type(pars_type), intent(in) :: pars
        real*8 :: c_CB1R
        real*8, intent(out) :: do_CB1R, dd_CB1R
        ! o_CB1R - open state probatility
        ! d_CB1R - the fraction of desensetisized or moved to extracellular compart state probatility
        ! c_CB1R - closed state probatility
        ! C <-alpha,beta-> O -gamma-> D -Epsilon-> C
        c_CB1R = 1-o_CB1R-d_CB1R
        do_CB1R = pars%CB1R%Alpha*eCB*c_CB1R - (pars%CB1R%Beta+pars%CB1R%Gamma)*o_CB1R
        dd_CB1R = -pars%CB1R%Epsilon*d_CB1R + pars%CB1R%Gamma*o_CB1R
    end subroutine do_dd_CB1R

end module CB1R

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