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Yet, how mild and strong fear memories differ in underlying biology is not well understood. We hypothesized that this distinction may not be exclusively the result of changes within specific brain regions, but rather the outcome of collective changes in connectivity across multiple regions within the neural network. To test this, rats were fear conditioned in protocols of varying intensities to generate mild or strong memories. Neuronal activation driven by recall was measured using c-fos immunohistochemistry in 12 brain regions implicated in fear learning and memory. The interregional coordinated brain activity was computed and graph-based functional networks were generated to compare how mild and strong fear memories differ at the systems level. Our results show that mild fear recall is supported by a well-connected brain network with small-world properties in which the amygdala is well-positioned to be modulated by other regions. In contrast, this connectivity is disrupted in strong fear memories and the amygdala is isolated from other regions. These findings indicate that the neural systems underlying mild and strong fear memories differ, with implications for understanding and treating disorders of fear dysregulation.<\/jats:p>","DOI":"10.7554\/elife.88172","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T06:56:36Z","timestamp":1687848996000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.88172","source":"Crossref","is-referenced-by-count":9,"title":["Network-level changes in the brain underlie fear memory strength"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3632-5566","authenticated-orcid":true,"given":"Josue","family":"Haubrich","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01pxwe438","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Psychology, McGill University","place":["Montr\u00e9al, Canada"]},{"id":[{"id":"https:\/\/ror.org\/04tsk2644","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurophysiology, Ruhr-University Bochum","place":["Bochum, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Nader","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01pxwe438","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Psychology, McGill University","place":["Montr\u00e9al, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2023,12,4]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/s41386-021-01155-7","article-title":"Prefrontal cortex, amygdala, and threat processing: implications for PTSD","volume":"47","author":"Alexandra Kredlow","year":"2022","journal-title":"Neuropsychopharmacology"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108107","article-title":"Rewarding information presented during reactivation attenuates fear memory: Methylphenidate and fear memory updating","volume":"171","author":"Arellano P\u00e9rez","year":"2020","journal-title":"Neuropharmacology"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.nlm.2004.02.004","article-title":"Footshock intensity and generalization in contextual and auditory-cued fear conditioning in the rat","volume":"81","author":"Baldi","year":"2004","journal-title":"Neurobiology of Learning and Memory"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"4893","DOI":"10.1038\/s41380-022-01758-6","article-title":"An epigenetic mechanism for over-consolidation of fear memories","volume":"27","author":"Barchiesi","year":"2022","journal-title":"Molecular Psychiatry"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"3747","DOI":"10.1073\/pnas.0400087101","article-title":"The architecture of complex weighted networks","volume":"101","author":"Barrat","year":"2004","journal-title":"PNAS"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/s41583-018-0038-8","article-title":"On the nature and use of models in network neuroscience","volume":"19","author":"Bassett","year":"2018","journal-title":"Nature Reviews. 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