Human beings are living longer than ever before and cognitive decline experienced by aged adults, such as compromise in cognitive flexibility, has been attracting more and more attention. One such example is the aging-related impairment of memory extinction. However, its underlying neural basis, especially the functional basis at the synapse level, is largely unknown. This study verifies that Pavlovian contextual fear memory extinction is impaired in aged mice. A large body of previous studies have shown that the infralimbic prefrontal cortex (ilPFC) plays a pivotal role in memory extinction. Correspondingly, this study reveals an aging-related reduction in the efficacy of excitatory synaptic transmission onto the ilPFC pyramidal neurons via electrophysiology recordings. This study further suggests that this reduced excitation potentially contributes to the aging-related impairment of contextual fear memory extinction: chemogenetically suppressing the activity of the ilPFC pyramidal neurons in young mice impairs contextual fear memory extinction, whereas chemogenetically compensating the reduced excitation of the ilPFC pyramidal neurons in aged mice restores contextual fear memory extinction. This study identifies a functional synaptic plasticity in the ilPFC pyramidal neurons that potentially contributes to the aging-related impairment of contextual fear memory extinction, which would potentially help to develop a therapy to treat related cognitive decline in aged human adults.

中文翻译：

---

边缘下前额叶皮质兴奋性突触传递功效的降低可能导致老年小鼠情境恐惧记忆消退的损害

人类的寿命比以往任何时候都长，老年人经历的认知衰退，例如认知灵活性的妥协，已经引起了越来越多的关注。一个这样的例子是记忆消退与衰老相关的损害。然而，其潜在的神经基础，尤其是突触水平的功能基础，在很大程度上是未知的。本研究证实巴甫洛夫语境恐惧记忆消退在老年小鼠中受损。大量先前的研究表明，下边缘前额叶皮层 (ilPFC) 在记忆消退中起着关键作用。相应地，这项研究通过电生理学记录揭示了与衰老相关的兴奋性突触传递到 ilPFC 锥体神经元的功效降低。这项研究进一步表明，这种减少的兴奋可能会导致与衰老相关的情境恐惧记忆消退的损害：化学遗传学抑制年轻小鼠 ilPFC 锥体神经元的活动会损害情境恐惧记忆消退，而化学遗传学补偿 ilPFC 锥体神经元的兴奋减少年老小鼠的神经元恢复情境恐惧记忆消退。这项研究确定了 ilPFC 锥体神经元中的功能性突触可塑性，这可能会导致与衰老相关的情境恐惧记忆消退损伤，这可能有助于开发一种治疗老年人相关认知能力下降的疗法。化学遗传学抑制年轻小鼠 ilPFC 锥体神经元的活动会损害情境恐惧记忆消退，而化学遗传学补偿老年小鼠 ilPFC 锥体神经元兴奋减少可恢复情境恐惧记忆消退。这项研究确定了 ilPFC 锥体神经元中的功能性突触可塑性，这可能会导致与衰老相关的情境恐惧记忆消退损伤，这可能有助于开发一种治疗老年人相关认知能力下降的疗法。化学遗传学抑制年轻小鼠 ilPFC 锥体神经元的活动会损害情境恐惧记忆消退，而化学遗传学补偿老年小鼠 ilPFC 锥体神经元兴奋减少可恢复情境恐惧记忆消退。这项研究确定了 ilPFC 锥体神经元中的功能性突触可塑性，这可能会导致与衰老相关的情境恐惧记忆消退损伤，这可能有助于开发一种治疗老年人相关认知能力下降的疗法。