Memory allows organisms to predict future events based on their prior sampling of the world. Rather than faithfully encoding each detail of related episodes, the brain is thought to incrementally construct probabilistic estimates of environmental statistics that are re-evaluated each time relevant events are encountered [1]. When faced with evidence that does not adequately fit mnemonic predictions, a process called reconsolidation can alter relevant memories to better recapitulate ongoing experience [2]. Conversely, when an ongoing event matches well-established predictions, reactivated memories tend to remain stable [3, 4]. In part, the brain may confer selective mnemonic stability by shifting cell-intrinsic mechanisms of plasticity induction [5], which could serve to constrain maladaptive updating of reliably predictive representations during anomalous events. Based on evidence of decreased cognitive flexibility and restricted synaptic plasticity in later life [6], we hypothesized that some prevalent age-associated neurobiological changes might in fact contribute to mnemonic stability [7]. Specifically, we predicted that amyloid beta (Aβ)-a peptide that often accumulates in the brains of individuals expressing senescent dementia [8-10]-is required for memory stabilization. Indeed, we observe elevated soluble Aβx-42 concentrations in the amygdala shortly after young adult rats form reconsolidation-resistant auditory fear memories. Suppressing secretases required for Aβ production immediately after learning prevents mnemonic stabilization, rendering these memories vulnerable to disruption by post-reactivation amnestic treatments. Thus, the seemingly pathogenic Aβ42 peptide may serve an adaptive physiological function during memory consolidation by engaging mechanisms that protect reliably predictive representations against subsequent modification.

中文翻译：

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巩固过程中分泌的淀粉样蛋白 β 可防止记忆延展性。

记忆使生物体能够根据他们先前对世界的采样来预测未来的事件。人们认为大脑不是忠实地编码相关事件的每个细节，而是逐步构建环境统计的概率估计，每次遇到相关事件时都会重新评估这些估计 [1]。当面临不完全符合助记预测的证据时，称为再巩固的过程可以改变相关记忆以更好地概括正在进行的经验 [2]。相反，当正在进行的事件与公认的预测相匹配时，重新激活的记忆往往会保持稳定 [3, 4]。在某种程度上，大脑可能通过改变可塑性诱导的细胞内在机制来赋予选择性记忆稳定性 [5]，这可以用于限制异常事件期间可靠预测表示的适应不良更新。基于晚年认知灵活性降低和突触可塑性受限的证据 [6]，我们假设一些普遍存在的与年龄相关的神经生物学变化实际上可能有助于记忆稳定性 [7]。具体来说，我们预测淀粉样蛋白 β (Aβ)——一种经常在表达衰老性痴呆症的个体的大脑中积累的肽 [8-10]——是记忆稳定所必需的。事实上，在年轻的成年大鼠形成抗再巩固的听觉恐惧记忆后不久，我们观察到杏仁核中可溶性 Aβx-42 浓度升高。在学习后立即抑制 Aβ 产生所需的分泌酶可防止记忆稳定，使这些记忆容易受到再激活后记忆删除治疗的破坏。因此，看似致病的 Aβ42 肽可以通过参与保护可靠预测表征免受后续修改的机制，在记忆巩固过程中发挥适应性生理功能。