美国国立卫生研究院Joshua A. Gordon、哥伦比亚大学Alan J. Park等研究人员合作发现，海马-前额叶回路的重置有助于学习。相关论文于2021年2月24日在线发表在《自然》杂志上。
研究人员表示，快速适应新情况的能力对于生存至关重要，而这种灵活性在许多神经精神疾病中均受到损害。因此，了解新鲜事物是否以及如何激发大脑回路来促进认知灵活性具有重要的转化意义。接触新鲜事物会招募海马和前额内侧皮层（mPFC），并可能引发海马-前额叶回路，从而促进随后的学习相关可塑性。
研究人员发现，新鲜事物重置了连接腹侧海马（vHPC）和mPFC的神经回路，从而促进了克服既定策略的能力。通过将vHPC活性重新组织为局部theta（4–12 Hz）振荡并削弱现有的vHPC-mPFC连接性将小鼠暴露于新鲜事物中会破坏以前的编码策略。随着小鼠随后适应新任务，vHPC神经元产生了与任务相关的新活动，vHPC-mPFC连接性得到增强，并且mPFC神经元被更新来编码新规则。
然而，当没有新鲜事物时，小鼠坚持其既定策略。阻断多巴胺D1受体（D1R）或抑制在vHPC中表达D1R的新鲜事物标签的细胞可阻止这些新的行为和生理效应。此外，D1R的激活模仿了新鲜事物的影响。这些结果表明，新鲜事物通过D1R介导的vHPC-mPFC回路复位来促进自适应学习，从而实现后续的学习相关回路可塑性。
附：英文原文
Title: Reset of hippocampal–prefrontal circuitry facilitates learning
Author: Alan J. Park, Alexander Z. Harris, Kelly M. Martyniuk, Chia-Yuan Chang, Atheir I. Abbas, Daniel C. Lowes, Christoph Kellendonk, Joseph A. Gogos, Joshua A. Gordon
Issue&Volume: 2021-02-24
Abstract: The ability to rapidly adapt to novel situations is essential for survival, and this flexibility is impaired in many neuropsychiatric disorders1. Thus, understanding whether and how novelty prepares, or primes, brain circuitry to facilitate cognitive flexibility has important translational relevance. Exposure to novelty recruits the hippocampus and medial prefrontal cortex (mPFC)2 and may prime hippocampal–prefrontal circuitry for subsequent learning-associated plasticity. Here we show that novelty resets the neural circuits that link the ventral hippocampus (vHPC) and the mPFC, facilitating the ability to overcome an established strategy. Exposing mice to novelty disrupted a previously encoded strategy by reorganizing vHPC activity to local theta (4–12 Hz) oscillations and weakening existing vHPC–mPFC connectivity. As mice subsequently adapted to a new task, vHPC neurons developed new task-associated activity, vHPC–mPFC connectivity was strengthened, and mPFC neurons updated to encode the new rules. Without novelty, however, mice adhered to their established strategy. Blocking dopamine D1 receptors (D1Rs) or inhibiting novelty-tagged cells that express D1Rs in the vHPC prevented these behavioural and physiological effects of novelty. Furthermore, activation of D1Rs mimicked the effects of novelty. These results suggest that novelty promotes adaptive learning by D1R-mediated resetting of vHPC–mPFC circuitry, thereby enabling subsequent learning-associated circuit plasticity.
DOI: 10.1038/s41586-021-03272-1
Source: https://www.nature.com/articles/s41586-021-03272-1
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
