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

Authors

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

Published in

Nature communications. Volume 17. Issue 1. Aug 04, 2026. Epub Aug 04, 2026.

Abstract

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.

PMID:
42552316
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.

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