Diversity of Spinal V1 Inhibitory Interneurons: Birthdates, Projections to Motoneurons, and Heterogeneity

Khái niệm cốt lõi

Spinal V1 inhibitory interneurons exhibit diversity in their timing of neurogenesis, synaptic targeting of motoneurons, and internal heterogeneity, with implications for their roles in motor control.

Tóm tắt

The content examines the diversity of spinal V1 inhibitory interneurons, a major group of ventral inhibitory interneurons that play crucial roles in shaping motor output. The key findings are:

Neurogenesis timing divides V1 interneurons into early-born (Renshaw cells, Pou6f2-V1s) and late-born (Foxp2-V1s, Sp8-V1s) clades. Early-born and late-born V1 clades settle in distinct positions in the ventral horn.

Foxp2-V1s, the largest V1 clade, contain over half of all V1 interneurons and provide the densest inhibitory input to motoneuron cell bodies, especially on limb-related lateral motor column (LMC) motoneurons.

Foxp2-V1s exhibit further heterogeneity, with subgroups differing in neurogenesis timing, proprioceptive input, and location relative to motor columns.

Renshaw cells and a subset of Foxp2-V1s form the majority of V1 synapses on motoneuron cell bodies and proximal dendrites, while other V1 clades (Pou6f2, Sp8) have minimal representation.

The diversity of V1 interneurons likely enables their distinct roles in motor control, with implications for understanding their ontogenetic and phylogenetic origins.

Thống kê

The number of Foxp2-V1s per 50 μm thick section (ventral horn) significantly increases in lower lumbar segments from L3 to L6 compared to S1.
The ratio of Foxp2-V1 neurons to motoneurons remains relatively constant at roughly 2.5:1 throughout the lumbar cord.

Trích dẫn

"Foxp2-V1 interneurons comprise 55.7% ±4.7 (mean±SD) of all genetically labeled Foxp2 neurons in the spinal cord."
"The highest density of Foxp2-V1 neurons cluster close to LMC motoneurons from L2 to L5."

Thông tin chi tiết chính được chắt lọc từ

SPINAL V1 INHIBITORY INTERNEURON CLADES DIFFER IN BIRTHDATE, PROJECTIONS TO MOTONEURONS AND HETEROGENEITY

by Worthy,A. E.... lúc www.biorxiv.org 12-01-2023

https://www.biorxiv.org/content/10.1101/2023.11.29.569270v1

Yêu cầu sâu hơn

How do the functional roles of early-born and late-born V1 clades differ in shaping motor output?

Early-born and late-born V1 clades play distinct roles in shaping motor output. Early-born V1 clades, such as Renshaw cells and Pou6f2-V1 interneurons, are primarily involved in modulating and patterning motoneuron firing to adjust the timing and force of muscle contractions. Renshaw cells, for example, are known for their recurrent feedback inhibition of motoneuron firing, contributing to the regulation of motor output. On the other hand, late-born V1 clades, including Foxp2-V1 and Sp8-V1 interneurons, have different functional roles. Foxp2-V1 interneurons, for instance, are tightly coupled to motoneurons, especially those related to limb motor pools, and provide dense and direct inhibitory synaptic input to motoneuron cell bodies. These interneurons are crucial in modulating locomotor speed, governing flexion-extension movements, and contributing to reciprocal inhibitory pathways. Overall, the early-born V1 clades are more involved in fundamental motor control functions, while the late-born V1 clades play a more specialized role in fine-tuning motor output, particularly in limb-related movements.

How do the potential developmental or evolutionary factors that have led to the increased size and heterogeneity of the Foxp2-V1 clade in mammals compared to earlier vertebrates?

The increased size and heterogeneity of the Foxp2-V1 clade in mammals compared to earlier vertebrates can be attributed to several potential developmental and evolutionary factors. One key factor is the complexity and diversification of motor control in mammals, particularly in limb-based terrestrial locomotion. As vertebrates transitioned from axial-swimming to limb-based locomotion, the demand for more sophisticated motor control systems increased, leading to the expansion and specialization of interneuron populations like the Foxp2-V1 clade. Evolutionary pressures for precise and coordinated movements in mammals likely drove the diversification and enlargement of the Foxp2-V1 clade to accommodate the intricate motor control requirements associated with limb movements.
Developmentally, the sequential neurogenesis of different V1 clades, with Foxp2-V1 interneurons being predominantly late-born, suggests a temporal regulation of interneuron generation that contributes to the increased heterogeneity of the Foxp2-V1 clade. The dynamic interplay between genetic lineage-tracing, synaptic connectivity, and circuit organization during development may have facilitated the expansion and specialization of the Foxp2-V1 clade in mammals. Additionally, the integration of proprioceptive inputs and reciprocal inhibitory pathways in Foxp2-V1 interneurons further enhances their functional diversity and complexity, reflecting the evolutionary adaptations for sophisticated motor control in mammals.

What are the implications of the close spatial association and synaptic targeting of Foxp2-V1 interneurons with limb-related motoneurons for understanding the neural control of voluntary movement?

The close spatial association and synaptic targeting of Foxp2-V1 interneurons with limb-related motoneurons have significant implications for understanding the neural control of voluntary movement, particularly in the context of limb-based locomotion in mammals. By forming dense and direct inhibitory synaptic connections with motoneuron cell bodies, especially in limb motor pools, Foxp2-V1 interneurons play a crucial role in modulating and fine-tuning motor output for limb movements. This close association suggests that Foxp2-V1 interneurons are key players in the coordination and regulation of voluntary movements, particularly those involving the limbs.
The specialized synaptic targeting of Foxp2-V1 interneurons on limb-related motoneurons indicates their involvement in precise motor control, such as adjusting the timing, force, and coordination of muscle contractions during limb movements. The integration of proprioceptive inputs and the establishment of reciprocal inhibitory pathways by Foxp2-V1 interneurons further highlight their role in feedback mechanisms and motor coordination. Understanding the specific contributions of Foxp2-V1 interneurons to limb motor control provides insights into the neural circuits and mechanisms underlying voluntary movement, offering valuable information for studying motor disorders, neurodegenerative diseases, and the evolution of motor control systems in mammals.