Revealing the role of the Direct and Indirect pathway in the striatum
For decades, the direct and indirect pathways of the basal ganglia have been thought to mediate behavioral promotion and inhibition, respectively. However, this classic dichotomous scientific model has been recently challenged. With in-vivo electrophysiology and an optogenetic tagging technique, Systems Neuroscience lab at KAIST (Professor Minwhan Jung) have elucidated complex encoding pattern of the two pathways in reward-based learning parameters and movement information. The findings provide new insights into striatal neural circuit operations.
The striatum is known to play crucial roles in diverse behavioral processes such as movement control and reward-based learning. Reinforcement learning is an algorithm which derives optimal strategies by calculating reward prediction error (RPE) from comparing expected value and the actual outcome. The agent can positively or negatively reinforce (avoid) choice with the reward prediction error. Also, the striatum is a well-known key structure responsible for voluntary movement control. Therefore, striatal circuits are vital neural circuits for living creatures to survive in the nature environment.
How well do we know about striatal circuits? Of a decades, the classic proposed model has been a holy grail in biological research in securing an understanding working mechanism of the striatum. The classic model of the function of the striatum involves the direct and indirect pathways which are anatomically segregated and have opposing roles in reward-based learning and movement control. (i) The direct pathway projects directly to the globus pallidus interna (GPi; in primates) and the substantia nigra pars reticulata (SNr). (ii) The indirect pathway projects to the globus pallidus externa (GPe) and then to the SNr/GPi. While the direct pathway SPNs (dSPNs) expresses dopamine D1 receptors, the indirect pathway SPNs (iSPNs) express dopamine D2 receptors.
From data from pharmacological modulation studies, activation of the direct pathway was known to initiate and provoke movement and provides positive reinforcement, whereas activation of the indirect pathway inhibits movement and provides negative reinforcement. This model was also a core mechanism to explain the pathophysiology of Parkinson’s disease and treatment.
However, there were recent findings that are not incorporated into classic models that assume antagonism between the direct and indirect pathways. Especially in the motor initiation, the direct and indirect pathways showed concurrent activation which opened the possibility that the two pathways may be a complementary. However, how dSPNs (D1 MSNs) and iSPNs (D2 MSNs) encode reward and movement-related information has not been studied.
The authors of this study hypothesized that reward and movement-related information in the direct and indirect pathway is encoded in a complex pattern rather than dichotomic pattern. They utilized a head-fixed classical conditioning task to test various types of related reward parameters. In the classic electrophysiologic recording, discriminating dSPNs and iSPNs in vivo was not possible, because they are electrophysiologically identical. Researchers could record D1 and D2 MSNs in-vivo with an optogenetic tagging technique.
As a result, this study showed that dSPNs tend to increase activity while iSPNs decrease activity as a function of reward value, suggesting the striatum represents value in the relative activity levels of dSPNs, versus iSPNs. Rapid responses to a negative outcome and previous reward-related responses are more frequent among iSPNs than dSPNs, suggesting stronger contributions of iSPNs to outcome-dependent behavioral adjustment. Most interestingly, an increase in lick offset-related activity is largely dSPN selective, suggesting dSPN involvement in suppressing ongoing licking behavior. When optogenetically stimulating dSPNs in freely moving condition, movement increased.
However when stimulating dSPNs during lick (goal-oriented behavior), lick was suppressed. These results suggested that the activation of dSPNs may modulate behavior in a context-dependent manner. Therefore, the study contributes to the idea that a much more complex and delicate model is required to explain the working mechanism of the basal ganglia.
For more information, please visit below paper link:https://www.nature.com/articles/s41467-017-02817-1
* lab webpage : https://sites.google.com/site/systemsneurolaboratory