美国加州大学医学院Kei M. Igarashi团队发现多巴胺促进内嗅皮层的联想记忆编码。这一研究成果发表在2021年9月22日出版的国际学术期刊《自然》上。
使用特定于细胞类型的电生理记录 ，他们显示来自腹侧被盖区和黑质的多巴胺信号控制外侧内嗅皮层 (LEC) 的 2a 层扇形细胞中提示-奖励关联规则的编码。当小鼠使用预先学习的关联规则学习新的嗅觉提示-奖励关联时，LEC扇形细胞的尖峰将新学习的奖励提示与预先学习的奖励提示分组，但将它们与预先学习的未奖励提示分开。扇形细胞的光遗传学抑制损害了新关联的学习，同时保留了对预先学习记忆的检索。
使用光纤光度计，他们发现多巴胺向 LEC 发送新诱导的奖励期望信号。LEC 多巴胺信号的抑制破坏了扇形细胞的关联编码并损害了学习性能。这些结果表明，LEC 粉丝细胞代表了抽象任务规则的认知图谱，而 LEC 多巴胺促进了新记忆与该图谱的结合。
据了解，越来越多的证据表明，纹状体中的多巴胺与基于奖励的强化学习密切相关。然而，目前尚不清楚多巴胺奖赏信号如何影响内嗅-海马回路，这是另一个对学习和记忆至关重要的大脑网络。
附：英文原文
Title: Dopamine facilitates associative memory encoding in the entorhinal cortex
Author: Lee, Jason Y., Jun, Heechul, Soma, Shogo, Nakazono, Tomoaki, Shiraiwa, Kaori, Dasgupta, Ananya, Nakagawa, Tatsuki, Xie, Jiayun L., Chavez, Jasmine, Romo, Rodrigo, Yungblut, Sandra, Hagihara, Meiko, Murata, Koshi, Igarashi, Kei M.
Issue&Volume: 2021-09-22
Abstract: Mounting evidence shows that dopamine in the striatum is critically involved in reward-based reinforcement learning1,2. However, it remains unclear how dopamine reward signals influence the entorhinal–hippocampal circuit, another brain network that is crucial for learning and memory3,4,5. Here, using cell-type-specific electrophysiological recording6, we show that dopamine signals from the ventral tegmental area and substantia nigra control the encoding of cue–reward association rules in layer 2a fan cells of the lateral entorhinal cortex (LEC). When mice learned novel olfactory cue–reward associations using a pre-learned association rule, spike representations of LEC fan cells grouped newly learned rewarded cues with a pre-learned rewarded cue, but separated them from a pre-learned unrewarded cue. Optogenetic inhibition of fan cells impaired the learning of new associations while sparing the retrieval of pre-learned memory. Using fibre photometry, we found that dopamine sends novelty-induced reward expectation signals to the LEC. Inhibition of LEC dopamine signals disrupted the associative encoding of fan cells and impaired learning performance. These results suggest that LEC fan cells represent a cognitive map of abstract task rules, and that LEC dopamine facilitates the incorporation of new memories into this map.
DOI: 10.1038/s41586-021-03948-8
Source: https://www.nature.com/articles/s41586-021-03948-8
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
