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

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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.
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;
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;
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 : Voltage-Dependent Calcium Channel L-type (1.3)
! converted from https://senselab.med.yale.edu/modeldb/showModel.cshtml?model=112834&file=%2Fnacb_msp%2FcaL13.mod (Wolf et al 2005)

module caL13

    use pars_mod
    use general_math
    use ghk_flux
    implicit none

    type caL13_tabs_type
        real*8, allocatable :: mtau(:), hinf(:), minf(:)
        integer :: n
        real*8 :: xst, xfin, xstep
    end type caL13_tabs_type

    type(caL13_tabs_type), save :: caL13_tabs


    subroutine caL13_tables_make(xst,xfin,n_x,pars, caL13_tabs)
        integer, intent(in) :: n_x
        real*8, intent(in) :: xst,xfin
        type(pars_type), intent(in) :: pars
        type(caL13_tabs_type), intent(out) :: caL13_tabs
        real*8 :: v, xstep
        real*8 :: malpha, mbeta
        integer :: i
        xstep = (xfin-xst)/n_x
        do i=1,n_x
            v = xst+xstep*(i-1)
            caL13_tabs%minf(i) = 1  /  ( 1 + exp( (v-pars%caL13%mvhalf-pars%caL13%mshift) / pars%caL13%mslope) )
            caL13_tabs%hinf(i) = 1  /  ( 1 + exp( (v-pars%caL13%hvhalf-pars%caL13%hshift) / pars%caL13%hslope) )
            ! to match caL13_tabs%hinf(i) data from Bell 2001, fig 2

            malpha = pars%caL13%c * (v-pars%caL13%vm) / ( exp((v-pars%caL13%vm)/pars%caL13%k) - 1 )
            mbeta = pars%caL13%cpr * exp(v/pars%caL13%kpr)! Kasai 1992, fig 15
            caL13_tabs%mtau(i) = 1 / (malpha + mbeta)
        end do
    end subroutine caL13_tables_make

    subroutine caL13_tables_clean(caL13_tabs)
        type(caL13_tabs_type) :: caL13_tabs
    end subroutine caL13_tables_clean

    real*8 function caL13_mtau(v)
        real*8, intent(in) :: v
        caL13_mtau=lin_interpTable_brds(caL13_tabs%mtau, caL13_tabs%n, (v-caL13_tabs%xst)/caL13_tabs%xstep)
    end function caL13_mtau

    real*8 function caL13_hinf(v)
        real*8, intent(in) :: v
        caL13_hinf=lin_interpTable_brds(caL13_tabs%hinf, caL13_tabs%n, (v-caL13_tabs%xst)/caL13_tabs%xstep)
    end function caL13_hinf

    real*8 function caL13_minf(v)
        real*8, intent(in) :: v
        caL13_minf=lin_interpTable_brds(caL13_tabs%minf, caL13_tabs%n, (v-caL13_tabs%xst)/caL13_tabs%xstep)
    end function caL13_minf

    real*8 function ical_caL13_func(v, h, m, calo, cali, pars)
        implicit none
        real*8 :: h, calo, m, cali, v
        type(pars_type) :: pars
        ical_caL13_func = ghk(v,cali,calo, pars) * pars%caL13%pcaLbar * m * m * h  ! Kasai 92, Brown 93
    end function ical_caL13_func

    subroutine dh_dm_caL13(v, h, m, pars, dh, dm)
        implicit none
        real*8, intent(in) :: v, h, m
        type(pars_type), intent(in) :: pars
        real*8, intent(out) :: dh, dm
        dh = (caL13_hinf(v) - h) / (pars%caL13%htau/pars%caL13%hqfact)
        dm = (caL13_minf(v) - m) / (caL13_mtau(v)/pars%caL13%qfact)
    end subroutine dh_dm_caL13

end module caL13

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