Large scale stochastic reaction-diffusion model of signaling pathways in a medium spiny projection neuron dendrite with spines to investigate whether the critical function of anchoring is to locate PKA near the cAMP that activates it or near its targets, such as AMPA receptors located in the post-synaptic density. Simulations, implemented in NeuroRD, show that PKA colocalization with adenylate cyclase, either in the spine head or in the dendrite, leads to greater phosphorylation of DARPP-32 Thr34 and AMPA receptor GluA1 Ser845 than when PKA is anchored away from adenylate cyclase.
Model Type: Molecular Network
Cell Type(s): Neostriatum medium spiny direct pathway GABA cell
Receptors: D1
Transmitters: Dopamine
Model Concept(s): Synaptic Plasticity; Signaling pathways
Simulation Environment: NeuroRD
Implementer(s): Blackwell, Avrama [avrama at gmu.edu]
References:
Oliveira RF, Kim M, Blackwell KT. (2012). Subcellular location of PKA controls striatal plasticity: stochastic simulations in spiny dendrites. PLoS computational biology. 8 [PubMed]