Abstract

In this study, we explore the functional role of striatal cholinergic interneurons, hereinafter referred to as tonically active neurons (TANs), via computational modeling; specifically, we investigate the mechanistic relationship between TAN activity and dopamine variations and how changes in this relationship affect reinforcement learning in the striatum. TANs pause their tonic firing activity after excitatory stimuli from thalamic and cortical neurons in response to a sensory event or reward information. During the pause striatal dopamine concentration excursions are observed. However, functional interactions between the TAN pause and striatal dopamine release are poorly understood. Here we propose a TAN activity-dopamine relationship model and demonstrate that the TAN pause is likely a time window to gate phasic dopamine release and dopamine variations reciprocally modulate the TAN pause duration. Furthermore, this model is integrated into our previously published model of reward-based motor adaptation to demonstrate how phasic dopamine release is gated by the TAN pause to deliver reward information for reinforcement learning in a timely manner. We also show how TAN-dopamine interactions are affected by striatal dopamine deficiency to produce poor performance of motor adaptation.

Highlights

  • It is widely accepted that the basal ganglia play an important role in action selection, the process by which contextually appropriate actions are chosen in response to presented stimuli

  • Our model provides a mechanistic interpretation of the tonically active neurons (TANs) activity-dopamine concentration relationship; we use our model to elucidate the mechanism by which striatal dopamine modulates the TAN pause duration, and how TAN activity regulates dopamine release

  • In this study we investigated the relationship between striatal dopamine and TAN activity; we elucidated the mechanism by which this interaction affects reinforcement learning in the striatum

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Summary

Introduction

It is widely accepted that the basal ganglia play an important role in action selection, the process by which contextually appropriate actions are chosen in response to presented stimuli. To determine the appropriateness of an action, in the basal ganglia perform reinforcement learning occurs to establish action-stimulus associations This learning process is facilitated by dopaminergic activity in the striatum, where a reward prediction error is encoded by the dopamine concentration excursion from its baseline level. Role of Striatal Tonically Active Neurons to appropriate stimulus-action association in the striatal network are strengthened by long-term potentiation, and inappropriate actions are suppressed by long-term depression (Frank, 2005; Graybiel, 2008). This process is well understood from a behavioral perspective, there are still open questions about the underlying neural circuitry

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