European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy; Department of Physics and Astronomy, University of Florence, Sesto Fiorentino, Italy.
European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy; Department of Physics and Astronomy, University of Florence, Sesto Fiorentino, Italy; National Institute of Optics - National Research Council (CNR-INO), Sesto Fiorentino, Italy.
Cell Rep. 2023 Aug 29;42(8):112908. doi: 10.1016/j.celrep.2023.112908. Epub 2023 Jul 29.
Fear responses are functionally adaptive behaviors that are strengthened as memories. Indeed, detailed knowledge of the neural circuitry modulating fear memory could be the turning point for the comprehension of this emotion and its pathological states. A comprehensive understanding of the circuits mediating memory encoding, consolidation, and retrieval presents the fundamental technological challenge of analyzing activity in the entire brain with single-neuron resolution. In this context, we develop the brain-wide neuron quantification toolkit (BRANT) for mapping whole-brain neuronal activation at micron-scale resolution, combining tissue clearing, high-resolution light-sheet microscopy, and automated image analysis. The robustness and scalability of this method allow us to quantify the evolution of activity patterns across multiple phases of memory in mice. This approach highlights a strong sexual dimorphism in recruited circuits, which has no counterpart in the behavior. The methodology presented here paves the way for a comprehensive characterization of the evolution of fear memory.
恐惧反应是功能适应性行为，会随着记忆而增强。事实上，详细了解调节恐惧记忆的神经回路可能是理解这种情绪及其病理状态的转折点。理解介导记忆编码、巩固和检索的回路提出了一个基本的技术挑战，即需要以单细胞分辨率分析整个大脑的活动。在这种情况下，我们开发了全脑神经元定量工具包（BRANT），用于以微米级分辨率绘制全脑神经元激活图，结合组织透明化、高分辨率光片显微镜和自动化图像分析。该方法的稳健性和可扩展性使我们能够量化小鼠记忆多个阶段的活动模式的演变。这种方法突出了募集回路中强烈的性别二态性，而在行为中则没有这种对应关系。本文提出的方法为全面描述恐惧记忆的演变铺平了道路。
