Dopamine Lesions Alter Striatal Encoding of Single-Limb Gait

Core Concepts

Striatal neurons encode gait on a single-limb and step basis, with dopamine depletion leading to stronger phase-locking in D2 MSNs.

Abstract

The study investigated the role of striatal neurons in encoding gait at a single-limb level. By combining video tracking, electrophysiology, and optogenetic tagging, it was found that both D1 and D2 MSNs were phase-locked to the gait cycle of individual limbs in mice. Healthy animals showed balanced limb phase-locking between D1 and D2 MSNs, while dopamine depletion led to stronger phase-locking in D2 MSNs. The findings suggest that striatal neurons represent gait on a single-limb and step basis, with elevated limb phase-locking of D2 MSNs potentially contributing to gait impairments associated with dopamine loss. The study also revealed insights into the neural mechanisms underlying impaired gait in conditions such as Parkinson's disease.

Stats

Dopamine depletion led to stronger phase-locking in D2 MSNs.
Around 45% of striatal neurons showed significant phase-locking to at least one limb.
In total, around 45% of striatal neurons showed significant phase-locking to at least one limb.
Unilateral 6OHDA lesions produced a strong asymmetry in gait.
Out of a total of 222 optogenetically tagged units, only 5 cells were excluded due to high vector length values.

Quotes

Key Insights Distilled From

Dopamine lesions alter the striatal encoding of single-limb gait

by Yang,L., Sin... at www.biorxiv.org 10-09-2023

https://www.biorxiv.org/content/10.1101/2023.10.06.561216v2

Deeper Inquiries

How do these findings contribute to our understanding of motor control beyond gait?

The findings from this study significantly contribute to our understanding of motor control beyond gait by revealing the intricate neural mechanisms involved in locomotion. By investigating the activity of D1 and D2 MSNs in relation to single-limb gait, the study sheds light on how different subpopulations of striatal neurons encode specific aspects of movement. This insight goes beyond traditional whole-body motion analysis and provides a more detailed picture of how individual limbs are coordinated during walking. Understanding the phase-locking properties of these neurons at a single-limb level offers valuable information about the fine-tuned control required for complex motor tasks.

What potential implications could the imbalance between D1 and D2 MSN activity have for other motor functions?

The imbalance between D1 and D2 MSN activity observed in this study could have significant implications for various other motor functions beyond gait. Given that these two populations play crucial roles in regulating movement initiation, speed, and coordination, an altered balance between them may impact a wide range of motor behaviors. For instance, disruptions in this balance could lead to difficulties in executing precise movements, impairments in coordinating multiple actions simultaneously, or challenges with initiating or stopping movements promptly. The findings suggest that maintaining an appropriate equilibrium between D1 and D2 MSN activity is essential for optimal motor function across different contexts.

How might studying single-limb gait provide insights into neurological disorders beyond Parkinson's disease?

Studying single-limb gait can offer valuable insights into neurological disorders beyond Parkinson's disease by providing a more nuanced understanding of how specific brain circuits are involved in controlling movement patterns. By examining the phase-locking properties of striatal neurons during individual limb motions, researchers can uncover subtle alterations that may underlie motor deficits seen in various conditions. For example, analyzing single-limb kinematics could help identify early markers or distinctive patterns associated with different neurological disorders such as Huntington's disease or cerebellar ataxia. Understanding how these diseases affect the coordination and rhythm of individual limbs during walking can enhance diagnostic accuracy, treatment strategies, and potentially pave the way for targeted interventions tailored to each disorder's unique neurophysiological signature.