Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Psychological and Brain Sciences, Boston University, Boston, MA, USA.
Neurobiol Aging. 2023 Mar;123:92-97. doi: 10.1016/j.neurobiolaging.2022.12.007. Epub 2022 Dec 22.
With the prevalence of age-related cognitive deficits on the rise, it is essential to identify cellular and circuit alterations that contribute to age-related memory impairment. Increased intrinsic neuronal excitability after learning is important for memory consolidation, and changes to this process could underlie memory impairment in old age. Some studies find age-related deficits in hippocampal neuronal excitability that correlate with memory impairment but others do not, possibly due to selective changes only in activated neural ensembles. Thus, we tagged CA1 neurons activated during learning and recorded their intrinsic excitability 5 hours or 7 days post-training. Adult mice exhibited increased neuronal excitability 5 hours after learning, specifically in ensemble (learning-activated) CA1 neurons. As expected, ensemble excitability returned to baseline 7 days post-training. In aged mice, there was no ensemble-specific excitability increase after learning, which was associated with impaired hippocampal memory performance. These results suggest that CA1 may be susceptible to age-related impairments in post-learning ensemble excitability and underscore the need to selectively measure ensemble-specific changes in the brain.
随着与年龄相关的认知能力下降的普遍出现,确定导致与年龄相关的记忆障碍的细胞和回路改变至关重要。学习后内在神经元兴奋性的增加对于记忆巩固很重要,而这个过程的变化可能是老年记忆障碍的基础。一些研究发现海马体神经元兴奋性与记忆障碍相关的年龄相关性缺陷,但其他研究则没有,这可能是由于仅在激活的神经集合体中发生选择性变化。因此,我们在学习过程中标记 CA1 神经元,并在训练后 5 小时或 7 天记录其内在兴奋性。成年小鼠在学习后 5 小时表现出神经元兴奋性增加,特别是在集合体(学习激活)CA1 神经元中。正如预期的那样,集合体兴奋性在训练后 7 天恢复到基线。在老年小鼠中,学习后没有集合体特异性兴奋性增加,这与海马体记忆表现受损有关。这些结果表明 CA1 可能容易受到与年龄相关的学习后集合体兴奋性损伤的影响,并强调需要选择性地测量大脑中的集合体特异性变化。