英语
神经科学
海马结构
背景(考古学)
齿状回
海马体
心理学
记忆形成
恐惧条件反射
记忆巩固
冻结行为
生物
扁桃形结构
古生物学
作者
Kaitlyn E. Dorst,Ryan A. Senne,Anh H. Diep,Antje R. de Boer,Rebecca L. Suthard,Héloïse Leblanc,Evan Ruesch,Angela Y. Pyo,Sara Skelton,Lucas C. Carstensen,Samantha Malmberg,Olivia McKissick,John Bladon,Steve Ramirez
标识
DOI:10.1523/jneurosci.0340-23.2023
摘要
Freezing is a defensive behavior commonly examined during hippocampal-mediated fear engram reactivation. How these cellular populations across different environmental demands engage the brain and modulate freezing is unclear. To address this, we optogenetically reactivated a fear engram in the dentate gyrus (DG) subregion of the hippocampus across three distinct contexts in male mice. We found that there were differential amounts of light-induced freezing depending on the size of the context in which reactivation occurred: mice demonstrated robust light-induced freezing in the most spatially restricted of the three contexts but not in the largest. We then utilized graph theoretical analyses to identify brain-wide alterations in cFos expression during engram reactivation across the smallest and largest contexts. Our manipulations induced positive interregional cFos correlations that were not observed in control conditions. Additionally, regions spanning putative “fear” and “defense” systems were recruited as hub regions in engram reactivation networks. Lastly, we compared the network generated from engram reactivation in the small context with a natural fear memory retrieval network. Here, we found shared characteristics such as modular composition and hub regions. By identifying and manipulating the circuits supporting memory function, as well as their corresponding brain-wide activity patterns, it is thereby possible to resolve systems-level biological mechanisms mediating memory's capacity to modulate behavioral states. Significance Statement Implementing appropriate defensive behaviors across disparate environments is essential for survival. Memories can be used to select these responses. Recent work identified and artificially manipulated cellular ensembles (i.e., memory engrams) within the hippocampus that mediate fear memory retrieval, yet how these populations engage brain-wide pathways that mediate defensive behaviors, such as freezing, under different environments is unclear. We demonstrated here that reactivation across environments of various sizes elicits different freezing responses and corresponding brain-wide network dynamics. These findings establish the flexibility of memory-bearing ensembles in generating brain and behavior states.
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