Harnessing a noncanonical vestibular input in the head-direction network to rectify age-related navigational deficits.

Navigational decline is a metric distinct from aging-related cognitive degradation, yet the affected circuits and synaptic changes remain elusive. This study identified a long-range excitatory projection from parvalbumin (PV) neurons in the brainstem medial vestibular nucleus (MVN) of mice that monosynaptically innervates the midbrain dorsal tegmental nucleus (DTN). This PV projection exhibits high neuronal excitability and synaptic plasticity as electrophysiological traits. In vivo chemogenetic inhibition of the PV projection impaired the navigational performance of adult mice. Navigational deficits in aged mice linked to both diminished innervation and synaptic drive of the PV pathway were pinpointed as hallmarks of the aging process. Strikingly, targeted activation of this pathway mitigated navigational impairments in older mice. In sum, our results revealed an excitatory PV pathway that impacts navigation. Rescue from aging-related navigational decline by activation of a spared projection pathway further highlights the potential for targeted therapies.