Scholarlink

<p>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<sup>MVN→DTN</sup> projection exhibits high neuronal excitability and synaptic plasticity as electrophysiological traits. In vivo chemogenetic inhibition of the PV<sup>MVN→DTN</sup> projection impaired the navigational performance of adult mice. Navigational deficits in aged mice linked to both diminished innervation and synaptic drive of the PV<sup>MVN→DTN</sup> 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<sup>MVN→DTN</sup> pathway that impacts navigation. Rescue from aging-related navigational decline by activation of a spared projection pathway further highlights the potential for targeted therapies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2025年5月28日

查看全文
  • Xiao-Qian Hu,
  • Kenneth Lap-Kei Wu,
  • Kang-Lin Rong,
  • Ya Ke,
  • Wing-Ho Yung,
  • Daisy Kwok-Yan Shum,
  • Ying-Shing Chan

摘要

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 PVMVN→DTN projection exhibits high neuronal excitability and synaptic plasticity as electrophysiological traits. In vivo chemogenetic inhibition of the PVMVN→DTN projection impaired the navigational performance of adult mice. Navigational deficits in aged mice linked to both diminished innervation and synaptic drive of the PVMVN→DTN 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 PVMVN→DTN pathway that impacts navigation. Rescue from aging-related navigational decline by activation of a spared projection pathway further highlights the potential for targeted therapies.