Impact of dopaminergic modulation on the state transitions of striatal medium spiny neuron sub-types - a computational study

Medium spiny neurons (MSN) of the striatum are known for their bistable membrane potential leading to two states: a hyperpolarized down-state and a depolarized up-state. Glutamatergic inputs from the hippocampus play a key role in switching the cell to the up-state. This gating is known to play a key role in regulating when other synaptic inputs, such as from the cortex, should generate action potentials and when they should be considered as noise. Any deviations from this pattern of state transitions indicates abnormal gating that has implications in conditions such as schizophrenia. Although dopamine is reported to modulate ion channels of MSN sub-types - dMSN and iMSN - its influence on the state transition times and up-state dwell times are not yet examined. We address this lacuna using biophysically constrained spiny models of dMSN and iMSN with explicit dopamine receptors. Our findings indicate a significant increase in up-state dwell time for dMSN and a significant decrease for iMSN when the % activation of DA receptors was increased. Additionally, a strong correlation between state transition times and spiking frequencies of MSN sub-types was observed.