Complementary Roles of D2-MSNs and D1-MSNs in Interval Timing

Core Concepts

D2-MSNs and D1-MSNs play complementary roles in interval timing, shaping temporal control of action.

Abstract

Abstract:

• Studied dorsomedial striatal cognitive processing during interval timing.
• D2-MSNs and D1-MSNs exhibit opposing dynamics over temporal intervals.
• Disrupting either D2-MSNs or D1-MSNs increases response times.

Introduction:

• Basal ganglia pathways play complex and complementary roles in movement.
• D2-MSNs and D1-MSNs have largely unknown roles in cognitive processing.
• Understanding basal ganglia cognitive processing is crucial for various diseases.

Results:

• D2-MSNs and D1-MSNs have opposite patterns of temporal encoding.
• Principal component analysis reveals time-dependent ramping activity.
• Disrupting D2-MSNs or D1-MSNs increases response times.

Drift-diffusion models:

• A four-parameter drift-diffusion model captures D2-MSN and D1-MSN dynamics.
• Disrupting either D2-MSNs or D1-MSNs increases response times.

Disrupting D2-MSNs or D1-MSNs:

• Optogenetic inhibition of D2-MSNs or D1-MSNs increases response times.
• Pharmacological disruption of D2-MSNs or D1-MSNs also increases response times.

MSN temporal encoding:

• Disrupting D2-MSNs or D1-MSNs degrades MSN temporal encoding.
• Temporal predictions are degraded with D2 or D1 blockade.

Stats

MSNs encode time across multiple intervals (Emmons et al., 2017; Gouvea et al., 2015; Mello et al., 2015).
D2-MSNs and D1-MSNs exhibit opposing dynamics during interval timing (Alexander and Crutcher, 1990; Cruz et al., 2022; Kravitz et al., 2010).
Disrupting D2-MSNs or D1-MSNs increases response times (De Corte et al., 2019; Drew et al., 2007; Stutt et al., 2023).

Quotes

"D2-MSNs and D1-MSNs have opposing patterns of activity with D2-MSNs ramping up and D1-MSNs ramping down." - Study Findings
"Disrupting either D2-MSNs or D1-MSNs increases response times, demonstrating their role in interval timing." - Research Conclusion

Key Insights Distilled From

Complementary cognitive roles for D2-MSNs and D1-MSNs in interval timing

by Bruce,R., We... at www.biorxiv.org 07-28-2023

https://www.biorxiv.org/content/10.1101/2023.07.25.550569v3

Deeper Inquiries

How do the findings of this study impact the development of treatments for diseases affecting the striatum

The findings of this study have significant implications for the development of treatments for diseases affecting the striatum. Understanding the complementary roles of D2-MSNs and D1-MSNs in interval timing provides valuable insights into how cognitive processes are regulated in the brain. This knowledge can be leveraged to develop targeted therapies for conditions such as Huntington's disease, Parkinson's disease, and schizophrenia, which are known to impact the striatum. By specifically targeting D2-MSNs or D1-MSNs based on their distinct roles in interval timing, novel treatment strategies can be developed to modulate cognitive functions in these diseases. Additionally, the study's use of optogenetics and pharmacological interventions highlights potential avenues for therapeutic interventions that can selectively target these specific neuronal populations in the striatum.

What are the potential implications of the complementary roles of D2-MSNs and D1-MSNs in interval timing for understanding human cognitive processes

The potential implications of the complementary roles of D2-MSNs and D1-MSNs in interval timing for understanding human cognitive processes are profound. The study reveals how these two distinct populations of neurons work together to shape temporal control of action, providing a deeper understanding of how cognitive functions are orchestrated in the brain. By demonstrating that D2-MSNs and D1-MSNs exhibit opposing dynamics but contribute complementary information to interval timing, the study sheds light on the intricate interplay between different neuronal populations in the basal ganglia. This knowledge can be extrapolated to human cognitive processes, offering insights into how the striatum may be involved in various cognitive functions beyond movement. Understanding the specific roles of D2-MSNs and D1-MSNs in interval timing can pave the way for further research into the neural mechanisms underlying cognitive processes in humans.

How might the results of this study influence future research on the basal ganglia and cognitive operations

The results of this study are poised to influence future research on the basal ganglia and cognitive operations in several ways. Firstly, the study's use of optogenetic tagging, computational modeling, and electrophysiology provides a comprehensive framework for investigating the neural dynamics underlying cognitive tasks such as interval timing. This approach can be extended to explore other cognitive functions and behaviors mediated by the basal ganglia, offering a more nuanced understanding of how different neuronal populations contribute to cognitive processing. Secondly, the identification of complementary roles for D2-MSNs and D1-MSNs in interval timing opens up new avenues for studying the functional organization of the basal ganglia and its implications for cognitive control. Future research can delve deeper into the specific mechanisms through which these neuronal populations interact and how their activity influences cognitive operations. Overall, the study sets the stage for further exploration of the basal ganglia's role in cognitive functions and may lead to novel discoveries in the field of neuroscience.