Review of Systems Biology Approaches: Detecting Signaling Pathways in Neurons

Temporal dynamics and spatial features are important factors in cell responses including synaptic plasticity. The complex network and interactions among neuronal signaling pathways result in emergent dynamical behaviors associated with synaptic plasticity. Signaling pathways can be activated by transmembrane receptors and result in transcription in the nucleus. For example, ionic channels and G protein coupled receptors may activate signaling pathway molecules and lead to electrical activities at various spatial and time scales (Blackwell, 2013). Functions of ionic channels can be altered by calcium at small temporal and spatial scales. Furthermore, functions of ionic channels can be altered by different kinases and phosphatases at larger temporal and spatial scales and result in synaptic plasticity.

Both experimental and computational methods for modeling neuronal signaling pathways have been suggested useful (Blackwell and Jedrzejewska-Szmek, 2013). For example, spatial models of signaling pathways have been related to extracellular signal-related kinase (ERK) activation among hippocampal neurons. Spatial models have also shown that anchoring proteins in synaptic plasticity play critical roles in putting molecules close to their activators. In addition, differences have been found between potentiation and depression among the spatial distribution of synaptic plasticity.

To better understand the functions of synaptic plasticity, it is needed to elucidate the roles of transmembrane receptors in stimulating ERK in neurons, as well as the targets of kinases. Challenges in the development of spatial models for synaptic plasticity include the estimation of parameter and the analyses of sensitivity (Blackwell and Jedrzejewska-Szmek, 2013). It is also necessary to simulate different reaction and diffusion events within various temporal and spatial scales (Blackwell, 2013). Systems biology approaches with interdisciplinary strategies would be helpful for meeting these challenges.


Blackwell KT. (2013) Approaches and tools for modeling signaling pathways and calcium dynamics in neurons. J Neurosci Methods. 2013 Jun 3.

Blackwell KT, Jedrzejewska-Szmek J. (2013) Molecular mechanisms underlying neuronal synaptic plasticity: systems biology meets computational neuroscience in the wilds of synaptic plasticity. Wiley Interdiscip Rev Syst Biol Med.

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