Program in Neurosciences & Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
Nat Neurosci. 2024 Sep;27(9):1794-1804. doi: 10.1038/s41593-024-01713-4. Epub 2024 Jul 19.
Across systems, higher-order interactions between components govern emergent dynamics. Here we tested whether contextual threat memory retrieval in mice relies on higher-order interactions between dorsal CA1 hippocampal neurons requiring learning-induced dendritic spine plasticity. We compared population-level Ca2 transients as wild-type mice (with intact learning-induced spine plasticity and memory) and amnestic mice (TgCRND8 mice with high levels of amyloid-β and deficits in learning-induced spine plasticity and memory) were tested for memory. Using machine-learning classifiers with different capacities to use input data with complex interactions, our findings indicate complex neuronal interactions in the memory representation of wild-type, but not amnestic, mice. Moreover, a peptide that partially restored learning-induced spine plasticity also restored the statistical complexity of the memory representation and memory behavior in Tg mice. These findings provide a previously missing bridge between levels of analysis in memory research, linking receptors, spines, higher-order neuronal dynamics and behavior.
在不同的系统中，组件之间的高阶相互作用控制着涌现的动力学。在这里，我们测试了在小鼠中，上下文威胁记忆检索是否依赖于需要学习诱导的树突棘可塑性的背侧 CA1 海马神经元之间的高阶相互作用。我们比较了群体水平的 Ca2+瞬变，当野生型小鼠（具有完整的学习诱导的棘突可塑性和记忆）和健忘型小鼠（TgCRND8 小鼠，具有高水平的淀粉样蛋白-β，并且在学习诱导的棘突可塑性和记忆方面存在缺陷）接受记忆测试时。使用具有不同能力的机器学习分类器来使用具有复杂相互作用的输入数据，我们的发现表明，在野生型小鼠的记忆表现中有复杂的神经元相互作用，但在健忘型小鼠中没有。此外，一种部分恢复学习诱导的棘突可塑性的肽也恢复了 Tg 小鼠记忆表现和记忆行为的统计复杂性。这些发现为记忆研究中的分析水平之间提供了一个以前缺失的桥梁，将受体、棘突、高阶神经元动力学和行为联系起来。
