Synaptic plasticity pathways

As discussed in the previous section, the motivation is to model the interaction between electrical activity in neurons and the synaptic proteome. This example (currently at shows how interactions between a number of ions, proteins and second messengers can be modeled.

Proteins involved

The full list of “agents” in the molecule_definitions.ka file is:

 1%agent: ca(x)
 2%agent: Glu(x)
 3%agent: NMDA(x, b0, b1, state~R~RA~RA2~d1~d2~2f~2s~o, type~A~B, mgb)
 4%agent: mg(x)
 5%agent: AMPA(x, loc~m~b~t, ser845~u~p, ser831~u~p, b1, b2, b3, b4, state~c0~c1~c2~c3~c4~d1~d2~d3~d4~o1~o2~o3~o4)
 6%agent: PMCA(x, cam)
 7%agent: NCX(x)
 8%agent: IMCBP(x)
 9%agent: CaB(h1, h2, h3, m1)
10%agent: CaM(site1, c1, c2, n1, n2)
11%agent: CaMKII(A, B, D, cam, sub, phos, Thr286~u~p, Thr305~u~p)
12%agent: NG(cam)
13%agent: CaN(cam, sub, m1, m2)
14%agent: AC1(cam)
15%agent: AC8(cam, camLoc~none~nLobe~cLobe)
16%agent: PDE1B(x, cam, phos~u~p)
17%agent: PDE4(x, pka, phos~u~p)
18%agent: cAMP(x)
19%agent: PKA(x, A1, B1, A2, B2, type~f~r~c) #full/regulatory/catalytic
20%agent: I1(x, thr35~u~p)
21%agent: PP1(x, i1)


These lines from the molecule_definitions.ka demonstrate how binding cAMP to PDE4 in an unphosphorylated state:

'PDE4 binding cAMP' PDE4(x, phos~u), cAMP(x) -> PDE4(x!1, phos~u), cAMP(x!1) @ 'PDE4cAMPk+'
'PDE4 unbinding cAMP' PDE4(x!1, phos~u), cAMP(x!1) -> PDE4(x, phos~u), cAMP(x) @ 'PDE4cAMPk-'
'PDE4 destroys cAMP' PDE4(x!1, phos~u), cAMP(x!1) -> PDE4(x, phos~u) @ 'PDE4cAMPcat'

These lines demonstrate phosphorylation of PDE4 by PKAc:

'PKAc phosphorylating PDE4' PKA(x!1, type~c), PDE4(x!1, phos~u) -> PKA(x, type~c), PDE4(x, phos~p) @ 'PKAPDE4cat'
'4Ca-CaM-CaN dephosphorylating PDE4 phos' CaN(cam!2, sub!1),
CaM(site1!2, c1!_, c2!_, n1!_, n2!_), PDE4(x!1, phos~p) ->
  CaN(cam!2, sub), CaM(site1!2, c1!_, c2!_, n1!_, n2!_), PDE4(x, phos~u) @ 'CaNPDE4cat'


The output of the simulation is shown below: