Miranda Magdalena, Navas Maria Carla, Zanoni Saad Maria Belen, Piromalli Girado Dinka, Weisstaub Noelia, Bekinschtein Pedro
Laboratory of Memory Research and Molecular Cognition, Institute for Cognitive and Translational Neuroscience, Universidad Favaloro, Instituto de Neurología Cognitiva and CONICET, Buenos Aires, Argentina.
Front Behav Neurosci. 2024 Oct 17;18:1478656. doi: 10.3389/fnbeh.2024.1478656. eCollection 2024.
Changes in memory performance are one of the main symptoms of normal aging. The storage of similar experiences as different memories (ie. behavioral pattern separation), becomes less efficient as aging progresses. Studies have focused on hippocampus dependent spatial memories and their role in the aging related deficits in behavioral pattern separation (BPS) by targeting high similarity interference conditions. However, parahippocampal cortices such as the perirhinal cortex are also particularly vulnerable to aging. Middle age is thought to be the stage where mild mnemonic deficits begin to emerge. Therefore, a better understanding of the timing of the spatial and object domain memory impairment could shed light over how plasticity changes in the parahipocampal-hippocampal system affects mnemonic function in early aging. In the present work, we compared the performance of young and middle-aged rats in both spatial (spontaneous location recognition) and non-spatial (spontaneous object recognition) behavioral pattern separation tasks to understand the comparative progression of these deficits from early stages of aging. Moreover, we explored the impact of environmental enrichment (EE) as an intervention with important translational value. Although a bulk of studies have examined the contribution of EE for preventing age related memory decline in diverse cognitive domains, there is limited knowledge of how this intervention could specifically impact on BPS function in middle-aged animals. Here we evaluate the effects of EE as modulator of BPS, and its ability to revert the deficits caused by normal aging at early stages. We reveal a domain-dependent impairment in behavioral pattern separation in middle-aged rats, with spatial memories affected independently of the similarity of the experiences and object memories only affected when the stimuli are similar, an effect that could be linked to the higher interference seen in this group. Moreover, we found that EE significantly enhanced behavioral performance in middle-aged rats in the spatial and object domain, and this improvement is specific of the high similarity load condition. In conclusion, these results suggest that memory is differentially affected by aging in the object and spatial domains, but that BPS function is responsive to an EE intervention in a multidomain manner.
记忆表现的变化是正常衰老的主要症状之一。随着衰老的进展，将相似经历存储为不同记忆（即行为模式分离）的效率会降低。研究通过针对高度相似的干扰条件，聚焦于海马体依赖的空间记忆及其在与衰老相关的行为模式分离（BPS）缺陷中的作用。然而，海马旁皮质，如嗅周皮质，也特别容易受到衰老的影响。中年被认为是轻度记忆缺陷开始出现的阶段。因此，更好地了解空间和物体领域记忆损伤的时间，可能有助于揭示海马旁 - 海马系统中的可塑性变化如何影响早期衰老中的记忆功能。在本研究中，我们比较了年轻和中年大鼠在空间（自发位置识别）和非空间（自发物体识别）行为模式分离任务中的表现，以了解这些缺陷从衰老早期开始的比较进展情况。此外，我们探讨了环境丰富化（EE）作为一种具有重要转化价值的干预措施的影响。尽管大量研究已经考察了EE对预防不同认知领域中与年龄相关的记忆衰退的作用，但对于这种干预如何具体影响中年动物的BPS功能，了解有限。在这里，我们评估EE作为BPS调节剂的作用，以及它在早期阶段逆转正常衰老引起的缺陷的能力。我们发现中年大鼠在行为模式分离中存在领域依赖性损伤，空间记忆受到影响，与经历的相似性无关，而物体记忆仅在刺激相似时受到影响，这种效应可能与该组中更高的干扰有关。此外，我们发现EE显著提高了中年大鼠在空间和物体领域的行为表现，并且这种改善在高相似性负荷条件下是特异性的。总之，这些结果表明，记忆在物体和空间领域受到衰老的影响不同，但BPS功能对EE干预具有多领域响应性。
