Distinct vestibular neuron subtypes contribute to navigation and motor coordination

Abstract

The vestibular system, referred to as the sixth sense, plays a vital role in spatial navigation and motor coordination, with the central vestibular nucleus as the first processing center. However, there is still much that remains unknown regarding the specific contributions from neuronal subtypes in the medial vestibular nucleus (MVN), particularly the parvalbumin-expressing (PV) and somatostatin-expressing (SST) neurons.

First, this study identified in mice an uncharted long-range projection of excitatory PVMVN neurons that directly innervate the midbrain dorsal tegmental nucleus (DTN) monosynaptically. It is further proved that this PVMVN→DTN projection is imperative for efficient navigational function. Moreover, both decreased number and diminished drive of PVMVN→DTN synapses were pinpointed as hallmarks of age-related navigational deficits. Notably, chemogenetic activation of this pathway ameliorated navigational decline in aged mice, as evidenced by increased accuracy in heading direction and effective switching of navigational strategies. In sum, these results demonstrated for the first time how a newly identified excitatory PV pathway from the brainstem participates in navigational circuits and changes along aging, suggesting a viable cellular candidate for targeted therapies that mitigate navigational impairments.

Second, this study also found that SST neurons within the MVN are essential for motor coordination. SST neurons contribute to the integration of sensory signals and modulation of downstream motor pathways, ensuring smooth and coordinated movements.

In summary, the segregated roles of PV and SST neurons in the MVN contribute to navigation and motor coordination, respectively. The PVMVN→DTN pathway is crucial for efficient navigation, and its dysregulation during aging underscores its potential as a cellular target for therapeutic interventions. Investigations into the roles of SST neurons further enhance our understanding of motor coordination mechanisms. These findings open exciting avenues for developing targeted therapies to address navigation and motor coordination impairments in various neurological conditions.