MCP Brain-IT: Computational modeling of intracellular signaling cascades in the basal ganglia

The striatum is the input layer of basal ganglia, a set of ancient brain nuclei involved in control of movements, action selection, reinforced learning and in pathologies like drug addiction and Parkinson disease. The striatum receives several chemical signals not only through projections from the cortex (glutamate) and midbrain (dopamine) but also from striatal interneurons like TAN (acetylcholine) and nNOS (NO).

Our project deals with the construction of computational models of the intracellular signaling dynamics triggered by these neurotransmitters and neuromodulators in all main cell types in the striatum, specially medium spiny neurons. These quantitative models are useful to challenge low resolution verbal models common among experimenters in order to disclose controversial issues and aid the design of new experiments. Furthermore, they can assist the rational development of therapies by revealing better targets. Big challenges in constructing these models are to find parameters for the reaction rates in the biochemical network, as well as validating the models. One part of validation consists of multi-parameter sensitivity analysis.