The network configuration in Parkinsonian state compensates network activity change caused by loss of dopamine.

Parkinson's disease is a movement disorder caused by dopamine depletion in the basal ganglia. Neural activity of the subthalamic nucleus (STN) and globus pallidus externus (GPe) in the basal ganglia are closely related to motor symptoms of Parkinson's disease. However, the pathogenesis of the disease and the transition from the normal state to the pathological state have yet to be elucidated. The functional organization of the GPe is gaining attention due to the recent finding that it consists of two distinct cell populations, namely prototypic GPe neurons and arkypallidal neurons. Identifying connectivity structures between these cell populations, as well as STN neurons, in relation to the dependence of the network activity on the dopaminergic effects is vital. In the present study, using a computational model of the STN-GPe network, we explored biologically plausible connectivity structures between these cell populations. We evaluated the experimentally reported neural activities of these cell types to elucidate the effects of dopaminergic modulation and changes caused by chronic dopamine depletion, such as strengthened connections in the neural activity of the STN-GPe network. Our results indicate that the arkypallidal neurons receive cortical inputs separately from the source for prototypic and STN neurons, suggesting that arkypallidal neurons might be responsible for an additional pathway with the cortex. Furthermore, changes caused by chronic dopamine depletion compensate for the loss of dopaminergic modulation. Changes caused by dopamine depletion itself likely induce the pathological activity observed in patients with Parkinson's disease. However, such changes counteract those of firing rates caused by loss of dopaminergic modulation. In addition, we observed that the STN-GPe tends to exhibit activity with pathological characteristics as side effects.