We use a combination of live cell imaging and stochastic modeling of signaling pathways to investigate how noradrenergic receptor stimulation interacts with calcium to control cAMP, required for synaptic plasticity and memory in the hippocampus. Our simulation results explain the mechanism whereby prior noradrenergic receptor stimulation does not enhance the subsequent NMDA stimulated cAMP elevation. Specifically, our results demonstrate the the negative feedback loop from cAMP, through PKA, to PDE4 cannot explain the results, and that switching of the noradrenergic receptor from Gs to Gi is required.
Model Type: Molecular Network
Cell Type(s): Hippocampus CA1 pyramidal GLU cell
Receptors: NMDA; Adrenergic
Transmitters: Norephinephrine
Model Concept(s): Synaptic Plasticity; Long-term Synaptic Plasticity; Signaling pathways; G-protein coupled; Reaction-diffusion
Simulation Environment: C or C++ program; Java; Python
Implementer(s): Blackwell, Avrama [avrama at gmu.edu]
References:
Chay A, Zamparo I, Koschinski A, Zaccolo M, Blackwell KT. (2016). Control of ßAR- and N-methyl-D-aspartate (NMDA) Receptor-Dependent cAMP Dynamics in Hippocampal Neurons. PLoS computational biology. 12 [PubMed]