Excitatory Spinal Lhx9-Derived Interneurons Modulate Locomotor Frequency in Mice.

Area of Science:

• Neuroscience
• Spinal Cord Research
• Motor Control

Background:

• Locomotion relies on spinal networks for rhythm and coordination.
• Existing research implicates several glutamatergic populations in mouse locomotor rhythm generation.
• These known populations represent a small fraction of excitatory spinal neurons.

Purpose of the Study:

• To identify novel excitatory spinal neuron populations involved in locomotor rhythm generation.
• To characterize the role of these newly identified neurons in motor control.

Main Methods:

• RNA sequencing of neonatal mouse spinal cord cells (glutamatergic, non-glutamatergic, Shox2).
• Differential gene expression analysis to identify transcription factors.
• Genetic ablation and optogenetic manipulation of Lhx9-derived neurons.
• In vivo calcium imaging during locomotor-like activity.

Main Results:

• Identified Lhx9-derived neurons as a distinct, purely glutamatergic, ipsilaterally projecting population.
• Ablation or inactivation of Lhx9-derived neurons decreased locomotor frequency without affecting coordination.
• Optogenetic activation modulated locomotor frequency, and calcium activity showed out-of-phase rhythmicity.

Conclusions:

• Lhx9-derived neurons are a novel population of spinal excitatory neurons regulating locomotor frequency.
• These neurons contribute to rhythm generation in the mammalian spinal cord.
• This discovery expands our understanding of the neural circuits underlying locomotion.