Data-driven multiscale modeling and simulation of the striatum

The research goal is to delineate the subcellular and cellular/network mechanisms underlying striatal involvement in selection of behaviour and reward learning.

This research is significant as striatum, the input stage of the basal ganglia, is involved in several neuropshychiatric conditions, such as drug addiction, Parkinson´s disease, etc.This project continues in parallell at different levels of biological organization - cellular/microcircuit and subcellular levels.

These levels are analysed through data-driven modeling and simulation, and in close interactions with experimentalists.We aim specifically to:1) further improve our biophysicaly detailed striatal microcircuit model consisting of both the direct- and indirect pathway striatal projection neurons (SPN), the fast spiking interneurons (FS), the low threshold spiking interneurons (LTS), the cholinergic interneurons (ChIN), etc.

The network is activated by simulated inputs from cortex, thalamus, the dopamine system, etc.

Also inputs from the arkypallidal population within globus pallidus externa will be added;2) model the receptor induced cascades in the corticostriatal synapses onto SPNs that are activated by glutamatergic (NMDA/AMPA, mGLuR), dopaminergic (D1R, D2R) and cholinergic (M4R, M1R) inputs. Successively the subcellular signaling models will become integrated into SPN models.

This will allow us to predict what types of synaptic activation patterns that lead to long term synaptic plasticity.