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<p>Postural and locomotor dysfunction represent axial symptoms of Parkinson’s disease (PD), which remain poorly treated by medication and deep brain stimulation. Whilst non-invasive neuromodulation of the vestibular system via the vestibular nucleus complex (VNC) offers a novel therapeutic avenue, the underlying circuits are still poorly characterized. Here we show that the mouse VNC feeds extensive <i>Vglut2</i>-defined projections into striato-thalamo-subthalamic and caudal medulla motor hubs and receives substantial input from the sensorimotor cortex. Optogenetic activation of excitatory VNC neurons at sub-symptomatic intensities increased <i>cFos</i>-based activity in basal ganglia-associated and brainstem motor targets. Unbiased pose dynamics and motion analysis respectively showed enhancement of behavioural modularity and locomotion with threshold-level stimulation. In a mouse model of PD, the latter further favored naturalistic gait patterns through improved motor coordination. Our data identify excitatory VNC processes as candidates for therapeutic targeting of axial motor dysfunction in the context of PD.</p>

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Vestibular nucleus stimulation for ameliorating locomotor dynamics in a Parkinsonian mouse model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月4日

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  • Johannes Hartig,
  • Maximilian Uwe Friedrich,
  • Jérémy Signoret-Genest,
  • Maria Gruber,
  • Sawako Tabuchi,
  • Hamidreza Alimohammadi,
  • Max Leuschner,
  • Nina Schöneberg,
  • Robert Peach,
  • Dennis Doll,
  • Tobias Petschner,
  • Amélie Neumann,
  • Susanne Knorr,
  • Jens Volkmann,
  • Philip Tovote,
  • Chi Wang Ip

摘要

Postural and locomotor dysfunction represent axial symptoms of Parkinson’s disease (PD), which remain poorly treated by medication and deep brain stimulation. Whilst non-invasive neuromodulation of the vestibular system via the vestibular nucleus complex (VNC) offers a novel therapeutic avenue, the underlying circuits are still poorly characterized. Here we show that the mouse VNC feeds extensive Vglut2-defined projections into striato-thalamo-subthalamic and caudal medulla motor hubs and receives substantial input from the sensorimotor cortex. Optogenetic activation of excitatory VNC neurons at sub-symptomatic intensities increased cFos-based activity in basal ganglia-associated and brainstem motor targets. Unbiased pose dynamics and motion analysis respectively showed enhancement of behavioural modularity and locomotion with threshold-level stimulation. In a mouse model of PD, the latter further favored naturalistic gait patterns through improved motor coordination. Our data identify excitatory VNC processes as candidates for therapeutic targeting of axial motor dysfunction in the context of PD.