Scientists propose a new theory on how basal ganglia control actions

In an ever-changing environment, choosing the right actions is crucial to an animal's survival and reproduction. The basal ganglia are a series of interconnected subcortical nuclei, including the striatum and substantia nigra, and numerous studies have shown that they play a major role in action selection. Clinically, many neurological and psychiatric diseases, including Parkinson's disease, Huntington's disease, obsessive-compulsive disorder, etc., are related to dysfunction of basal ganglia circuits. One of their common features is major defects in action selection and motor control. Anatomically, the basal ganglia control movement through two major pathways, the direct and indirect pathways, which originate from spiny projection neurons in the striatum that express D1 and D2 receptors, respectively. The classic textbook theory holds that the direct and indirect pathways of the basal ganglia are in opposition to each other, promoting and inhibiting target movements respectively (the "Go/No-go" model). However, in recent years, there have been different views in the field. It is believed by some researchers that the direct pathway selects target actions, while the indirect pathway inhibits other competing behaviors to enhance the target selection. The two pathways are thus not antagonistic but promoted to a collaborative relationship (the "Co-activation" model).

Figure 1. Mice choose actions based on internally-monitored time passage and the underlying neuronal activity in striatum.

A team led by Institute faculty, Prof. Xin Jin, has developed a new action selection behavioral paradigm, by training mice to select a specific one out two actions to perform based on self-estimated time interval length to receive a reward (Figure 1). Through multi-channel electrophysiological recording, optogenetic manipulation and behavioral analysis, they found that the neuronal activity of direct and indirect pathways in the basal ganglia alone cannot distinguish the different functional models mentioned above. Interestingly, they further found that some behavioral manipulation results were consistent with the predictions of the classic "Go/No-go" model, but inconsistent with the theory of the "Co-activation" model. However, while other parts of the behavioral manipulation results are at odds with the predictions of the classic "Go/No-go" model, they can be explained by the "Co-activation" model. In order to resolve these contradictions, Prof. Jin’s team proposed a new Center (D1 pathway) - Surround (D2 pathway #1) - Context (D2 pathway #2) "Triple-control" model based on the experimental data and neuroanatomy, in which there are two interacting indirect pathway sub-circuitries that dynamically exert opposing controls on basal ganglia output. In the new "Triple-control" model, the indirect pathway can dynamically participate in motor control, sometimes antagonizing the direct pathway (similar to the "Go/No-go" model), and at other times cooperating with the direct pathway (similar to the "Co-activation" model), depending on the network inputs and animal states.

Figure 2. A new "Triple-control" model of basal ganglia for action control.

It is worth noting that the new "Triple-control" model suggests that there exists an inverted U-shaped relationship between indirect pathway (D2) activation, as well as dopamine concentration, and behavioral decisions. That is, there is an optimal range of D2 and dopamine activities for action control (Figure 2). These results significantly advance our current understanding of how the basal ganglia control behavior, and have important implications for the pathology of a variety of motor and psychiatric disorders and their pharmacological treatments. This work was published on the international journal "eLife" 12: RP87644 (2023) under the title "Multiple dynamic interactions from basal ganglia direct and indirect pathways mediate action selection".  

Journal Reference:

Li, H., & Jin, X*. (2023). Multiple dynamic interactions from basal ganglia direct and indirect pathways mediate action selection. eLife, 12: RP87644.

>> To read the article in Chinese at the School of Life Sciences, East China Normal University, click here.