title: A network model of basal ganglia for understanding the roles of dopamine and serotonin in reward-punishment-risk based decision making.
abstract: There is significant evidence that in addition to reward-punishment based decision making, the Basal Ganglia (BG) contributes to risk-based decision making (Balasubramani et al., 2014). Despite this evidence, little is known about the computational principles and neural correlates of risk computation in this subcortical system. We have previously proposed a reinforcement learning (RL)-based model of the BG that simulates the interactions between dopamine (DA) and serotonin (5HT) in a diverse set of experimental studies including reward, punishment and risk based decision making (Balasubramani et al., 2014). Starting with the classical idea that the activity of mesencephalic DA represents reward prediction error, the model posits that serotoninergic activity in the striatum controls risk-prediction error. Our prior model of the BG was an abstract model that did not incorporate anatomical and cellular-level data. In this work, we expand the earlier model into a detailed network model of the BG and demonstrate the joint contributions of DA-5HT in risk and reward-punishment sensitivity. At the core of the proposed network model is the following insight regarding cellular correlates of value and risk computation. Just as DA D1 receptor (D1R) expressing medium spiny neurons (MSNs) of the striatum were thought to be the neural substrates for value computation, we propose that DA D1R and D2R co-expressing MSNs are capable of computing risk. Though the existence of MSNs that co-express D1R and D2R are reported by various experimental studies, prior existing computational models did not include them. Ours is the first model that accounts for the computational possibilities of these co-expressing D1R-D2R MSNs, and describes how DA and 5HT mediate activity in these classes of neurons (D1R-, D2R-, D1R-D2R- MSNs). Starting from the assumption that 5HT modulates all MSNs, our study predicts significant modulatory effects of 5HT on D2R and co-expressing D1R-D2R MSNs which in turn explains the multifarious functions of 5HT in the BG. The experiments simulated in the present study relates 5HT to risk sensitivity and reward-punishment learning. Furthermore, our model is shown to capture reward-punishment and risk based decision making impairment in Parkinson's Disease (PD). The model predicts that optimizing 5HT levels along with DA medications might be essential for improving the patients' reward-punishment learning deficits.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Madras Chennai, India.
authors.forename: Pragathi P
authors.initials: PP
authors.lastname: Balasubramani
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Madras Chennai, India.
authors.forename: V Srinivasa
authors.initials: VS
authors.lastname: Chakravarthy
authors.affiliation: Department of Computer Science and Engineering, Indian Institute of Technology Madras Chennai, India.
authors.forename: Balaraman
authors.initials: B
authors.lastname: Ravindran
authors.affiliation: School of Social Sciences and Technology, Marcs Institute for Brain and Behavior, University of Western Sydney Penrith, NSW, Australia ; Department of Veterans Affairs, New Jersey Health Care System East Orange, NJ, USA.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Moustafa
keywords: D1 and D2 receptor co-expression; basal ganglia network; dopamine; medium spiny neurons; punishment; reward; risk; serotonin