wawasan - Neuroscience - # Vestibulo-ocular reflex circuit development

Extraocular Motor Neurons Are Dispensable for the Assembly of a Sensorimotor Circuit Controlling Gaze Stabilization

Q: What other potential sources of signals, beyond motor neurons, could specify the fate and sensory input specificity of projection neurons in the vestibulo-ocular reflex circuit

In addition to motor neurons, several other potential sources of signals could specify the fate and sensory input specificity of projection neurons in the vestibulo-ocular reflex circuit. One key source could be the sensory afferents themselves. Sensory input from the vestibular system provides critical information about head and body position, which is essential for gaze stabilization. The directional tuning of sensory afferents innervating the projection neurons could play a role in specifying the subtype fate of these neurons. Additionally, interneurons within the circuit, such as those in the tangential nucleus, could also contribute to the specification of projection neuron fate. These interneurons may provide local cues or signals that influence the connectivity and function of projection neurons. Furthermore, molecular gradients or signaling pathways present during development could also play a role in guiding the fate and connectivity of projection neurons in the vestibulo-ocular reflex circuit.

Q: How might the loss of specific motor neuron pools (e.g., those controlling downward eye movements) impact the connectivity and function of their corresponding projection neuron partners

The loss of specific motor neuron pools, such as those controlling downward eye movements, could have significant impacts on the connectivity and function of their corresponding projection neuron partners in the vestibulo-ocular reflex circuit. In the absence of these motor neuron pools, the projection neurons that normally innervate these muscles may not receive the appropriate synaptic inputs required for proper function. This could lead to disruptions in the directional selectivity of projection neurons, affecting their ability to respond to specific tilt sensations and stabilize gaze effectively. Additionally, the absence of motor neuron pools controlling downward eye movements could result in imbalances in the activation of ocular muscles, leading to impaired eye movements and potentially affecting the overall functionality of the reflex circuit.

Q: Could the developmental mechanisms uncovered in this study for the vestibulo-ocular reflex circuit apply more broadly to other sensorimotor circuits, such as those involved in limb movement or postural control

The developmental mechanisms uncovered in this study for the vestibulo-ocular reflex circuit could potentially apply more broadly to other sensorimotor circuits involved in limb movement or postural control. The findings suggest that the fate specification and connectivity of projection neurons can develop independently of motor partners, highlighting the intrinsic mechanisms at play in circuit assembly. This concept could be extrapolated to other sensorimotor circuits, where the precise connectivity between sensory and motor components is crucial for generating appropriate behavioral responses. Understanding how projection neurons establish connectivity and functional specificity in the absence of motor-derived signals could provide insights into the general principles of neural development across different sensorimotor systems. By investigating similar mechanisms in other circuits, researchers may uncover shared developmental strategies that underlie the formation of complex sensorimotor behaviors.

Konsep Inti

Motor neurons are not required for the proper connectivity, anatomical assembly, or transcriptional profiles of central projection neurons in the sensorimotor circuit for gaze stabilization.

Abstrak

The study investigates whether motor neurons play an instructive role in specifying the fate and connectivity of pre-motor projection neurons in the vestibulo-ocular reflex circuit for gaze stabilization.

Key findings:

Projection neurons in the tangential nucleus develop normal directional selectivity and topography in response to vestibular sensory inputs, even in the absence of extraocular motor neurons.
Projection neurons remain anatomically and molecularly competent to assemble with appropriate motor targets, despite the lack of motor partners.
The transcriptional profiles of projection neurons are largely unchanged in the absence of motor neurons.

These results overturn the long-standing "retrograde" model, which posits that motor neurons instruct the fate and connectivity of their pre-motor partners. Instead, the signals that specify projection neuron fate and sensory input specificity must lie elsewhere, potentially in intrinsic genetic mechanisms or extrinsic sources beyond motor neurons.

The study provides causal evidence against an instructional role of motor neurons in sensorimotor circuit assembly and advances our understanding of general principles governing neural development.

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Statistik

"In phox2a mutants, we observed an expected and near-total loss of isl1 expression (WT: 298±19 neurons across both hemispheres; null: 19±11 neurons; Wilcoxon rank sum test, p=2.5×10−4) at 5 dpf, well-after nIII/nIV differentiation is complete."
"Projection neurons responded to tilt sensations with comparable magnitudes (nose-down mean ΔFF, sib: 1.86±1.69; phox2a: 2.07±1.48; two-tailed Wilcoxon rank sum test, p=0.98; nose-up mean ΔFF, sib: 1.24±1.23; phox2a: 1.02±0.89; p=0.18)."
"Directional selectivity remained unchanged in phox2a mutants (nose-down mean index, sib: 0.73±0.29; phox2a: 0.68±0.29; two-tailed Wilcoxon rank sum test, p=0.85; nose-up mean index, sib: 0.85±0.26; phox2a: 0.81±0.29; p=0.12)."

Kutipan

"Our findings comprehensively overturn a long-standing model: that connectivity in the circuit for gaze stabilization is retrogradely determined by motor partner-derived signals."
"More broadly, our work argues against a deterministic role of motor neurons in specifying the fate and sensory connectivity of pre-motor circuit components."

Wawasan Utama Disaring Dari

Motor neurons are dispensable for the assembly of a sensorimotor circuit for gaze stabilization

by Goldblatt,D.... pada www.biorxiv.org 01-27-2024

https://www.biorxiv.org/content/10.1101/2024.01.25.577261v1

Pertanyaan yang Lebih Dalam

What other potential sources of signals, beyond motor neurons, could specify the fate and sensory input specificity of projection neurons in the vestibulo-ocular reflex circuit

In addition to motor neurons, several other potential sources of signals could specify the fate and sensory input specificity of projection neurons in the vestibulo-ocular reflex circuit. One key source could be the sensory afferents themselves. Sensory input from the vestibular system provides critical information about head and body position, which is essential for gaze stabilization. The directional tuning of sensory afferents innervating the projection neurons could play a role in specifying the subtype fate of these neurons. Additionally, interneurons within the circuit, such as those in the tangential nucleus, could also contribute to the specification of projection neuron fate. These interneurons may provide local cues or signals that influence the connectivity and function of projection neurons. Furthermore, molecular gradients or signaling pathways present during development could also play a role in guiding the fate and connectivity of projection neurons in the vestibulo-ocular reflex circuit.

How might the loss of specific motor neuron pools (e.g., those controlling downward eye movements) impact the connectivity and function of their corresponding projection neuron partners

The loss of specific motor neuron pools, such as those controlling downward eye movements, could have significant impacts on the connectivity and function of their corresponding projection neuron partners in the vestibulo-ocular reflex circuit. In the absence of these motor neuron pools, the projection neurons that normally innervate these muscles may not receive the appropriate synaptic inputs required for proper function. This could lead to disruptions in the directional selectivity of projection neurons, affecting their ability to respond to specific tilt sensations and stabilize gaze effectively. Additionally, the absence of motor neuron pools controlling downward eye movements could result in imbalances in the activation of ocular muscles, leading to impaired eye movements and potentially affecting the overall functionality of the reflex circuit.

Could the developmental mechanisms uncovered in this study for the vestibulo-ocular reflex circuit apply more broadly to other sensorimotor circuits, such as those involved in limb movement or postural control

The developmental mechanisms uncovered in this study for the vestibulo-ocular reflex circuit could potentially apply more broadly to other sensorimotor circuits involved in limb movement or postural control. The findings suggest that the fate specification and connectivity of projection neurons can develop independently of motor partners, highlighting the intrinsic mechanisms at play in circuit assembly. This concept could be extrapolated to other sensorimotor circuits, where the precise connectivity between sensory and motor components is crucial for generating appropriate behavioral responses. Understanding how projection neurons establish connectivity and functional specificity in the absence of motor-derived signals could provide insights into the general principles of neural development across different sensorimotor systems. By investigating similar mechanisms in other circuits, researchers may uncover shared developmental strategies that underlie the formation of complex sensorimotor behaviors.