Chemogenetic Manipulation of Purkinje Cells Reveals Their Role in Postural Control in Larval Zebrafish

Khái niệm cốt lõi

Purkinje cells in the cerebellum play a crucial role in regulating postural control and fin-body coordination during swimming in larval zebrafish.

Tóm tắt

The study used a chemogenetic approach to manipulate Purkinje cells in the cerebellum of larval zebrafish and examined the effects on posture and locomotion.
Key highlights:

Activation of Purkinje cells disrupted postural control, leading to more nose-up or nose-down postures during climbing and diving behaviors.
Ablation of Purkinje cells also disrupted postural control, with more pronounced effects in older larvae, suggesting an emerging role for the cerebellum in postural maturation.
Purkinje cell ablation impaired the speed-dependent coordination between the fins and trunk, which is crucial for effective climbing.
Purkinje cell activity could encode the direction of pitch tilt, both at the individual neuron and population levels, with a shift in the preferred tuning direction observed across development.
The study establishes a powerful new chemogenetic approach to manipulate cerebellar output and quantify its contributions to unconstrained postural and locomotor behaviors in larval zebrafish.

Thống kê

"Activation disrupted postural control in the pitch (nose-up/nose-down) axis."
"Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs."
"After Purkinje cell lesion, the average climb posture increased 36% relative to controls."
"After Purkinje cell lesion, the average dive posture was 24% more negative than in control animals."
"Speed-dependent increases in lift with greater trunk rotation are disrupted after Purkinje cell loss."

Trích dẫn

"Activation disrupted postural control in the pitch (nose-up/nose-down) axis."
"Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs."
"Postural disruption was more widespread in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture."

Thông tin chi tiết chính được chắt lọc từ

Cerebellar Purkinje Cells Control Posture in Larval Zebrafish (Danio rerio)

by Auer,F., Nar... lúc www.biorxiv.org 09-14-2023

https://www.biorxiv.org/content/10.1101/2023.09.12.557469v2

Yêu cầu sâu hơn

How do the developmental changes in Purkinje cell tuning direction and population coding relate to the emergence of more pronounced postural deficits in older larvae

The developmental changes in Purkinje cell tuning direction and population coding are closely related to the emergence of more pronounced postural deficits in older larvae. At 7 days post-fertilization (dpf), there was an asymmetry in the tuning direction of Purkinje cells, with more cells being tuned to the nose-down direction. This tuning direction shifted between 7 and 14 dpf, with more cells becoming nose-up tuned at 14 dpf. This shift in tuning direction suggests a developmental refinement in how navigation in the pitch axis is processed in the cerebellum. As older larvae grow and develop, the changes in Purkinje cell tuning direction may reflect a more specialized and precise encoding of pitch direction, which is crucial for maintaining proper posture and balance. The shift towards more nose-up tuned cells at 14 dpf may indicate a maturation of the cerebellar circuitry involved in postural control, leading to more pronounced deficits in posture when Purkinje cells are manipulated in older larvae.

What are the downstream targets of Purkinje cells that mediate the observed effects on posture and fin-body coordination, and how do their response properties change across development

The downstream targets of Purkinje cells that mediate the observed effects on posture and fin-body coordination include vestibular nuclei and eurydendroid cells. Purkinje cells in the lateral cerebellum project to vestibular nuclei, which are involved in encoding posture and balance. The inhibitory output of Purkinje cells plays a crucial role in regulating the activity of these target nuclei, influencing the corrective pitch-axis behaviors necessary for maintaining stability. Additionally, Purkinje cells involved in locomotion converge on eurydendroid cells, which are responsible for coordinating trunk and fin movements during climbing. The disruption of Purkinje cell activity can lead to a disinhibition of these downstream targets, affecting the coordination of body and fin movements necessary for effective climbing. Across development, the response properties of these downstream targets may change to accommodate the maturation of postural control strategies in older larvae, reflecting the developmental refinement of cerebellar circuits involved in posture and coordination.

Could the chemogenetic approach be combined with whole-brain imaging to reveal the broader cerebellar and extra-cerebellar circuits involved in postural control and their maturation over time

The chemogenetic approach used in the study, involving TRPV1/capsaicin-mediated activation and ablation of Purkinje cells, could be combined with whole-brain imaging to reveal the broader cerebellar and extra-cerebellar circuits involved in postural control and their maturation over time. By integrating chemogenetic manipulation with advanced imaging techniques such as calcium imaging or voltage imaging, researchers can map the activity of Purkinje cells and their downstream targets in real-time across the entire brain. This comprehensive approach would provide insights into how Purkinje cell activity influences not only local cerebellar circuits but also broader neural networks involved in postural control. By tracking the changes in neural activity patterns in response to Purkinje cell manipulation at different developmental stages, researchers can uncover the maturation of cerebellar and extra-cerebellar circuits involved in postural control and gain a deeper understanding of the mechanisms underlying postural deficits in older larvae.