Deep space travel presents a number of measurable risks including exposure to a spectrum of radiations of varying qualities, termed galactic cosmic radiation (GCR) that are capable of penetrating the spacecraft, traversing through the body and impacting brain function. Using rodents, studies have reported that exposure to simulated GCR leads to cognitive impairments associated with changes in hippocampus function that can persist as long as one-year post exposure with no sign of recovery. Whether memory can be updated to incorporate new information in mice exposed to GCR is unknown. Further, mechanisms underlying long lasting impairments in cognitive function as a result of GCR exposure have yet to be defined. Here, we examined whether whole body exposure to simulated GCR using 6 ions and doses of 5 or 30 cGy interfered with the ability to update an existing memory or impact hippocampal synaptic plasticity, a cellular mechanism believed to underlie memory processes, by examining long term potentiation (LTP) in acute hippocampal slices from middle aged male mice 3.5–5 months after radiation exposure. Using a modified version of the hippocampus-dependent object location memory task developed by our lab termed “Objects in Updated Locations” (OUL) task we find that GCR exposure impaired hippocampus-dependent memory updating and hippocampal LTP 3.5–5 months after exposure. Further, we find that impairments in LTP are reversed through one-time systemic subcutaneous injection of the histone deacetylase 3 inhibitor RGFP 966 (10 mg/kg), suggesting that long lasting impairments in cognitive function may be mediated at least in part, through epigenetic mechanisms.

深空旅行存在许多可测量的风险，包括暴露于不同质量的辐射谱，称为银河宇宙辐射（GCR），它们能够穿透航天器、穿过身体并影响大脑功能。使用啮齿类动物进行的研究表明，接触模拟 GCR 会导致与海马体功能变化相关的认知障碍，这种情况可能会持续一年，而且没有恢复的迹象。暴露于 GCR 的小鼠的记忆是否可以更新以纳入新信息尚不清楚。此外，GCR 暴露导致认知功能长期受损的机制尚未明确。在这里，我们通过检查长期增强作用，检查了全身暴露于使用 6 种离子和 5 或 30 cGy 剂量的模拟 GCR 是否会干扰更新现有记忆的能力或影响海马突触可塑性（一种被认为是记忆过程基础的细胞机制） （LTP）在辐射暴露后 3.5-5 个月的中年雄性小鼠的急性海马切片中。使用我们实验室开发的海马依赖性物体位置记忆任务的修改版本，称为“更新位置的物体”（OUL）任务，我们发现 GCR 暴露在暴露后 3.5-5 个月损害了海马依赖性记忆更新和海马 LTP。此外，我们发现通过一次性全身皮下注射组蛋白脱乙酰酶 3 抑制剂 RGFP 966（10 mg/kg）可以逆转 LTP 损伤，这表明认知功能的长期持续损伤可能至少部分是通过表观遗传介导的。机制。