The microbiota regulate neuronal function and fear extinction learning

Coco Chu, Mitchell H. Murdock, Deqiang Jing, Tae Hyung Won, Hattie Chung, Adam M. Kressel, Tea Tsaava, Meghan E. Addorisio, Gregory G. Putzel, Lei Zhou, Nicholas J. Bessman, Ruirong Yang, Saya Moriyama, Christopher N. Parkhurst, Anfei Li, Heidi C. Meyer, Fei Teng, Sangeeta S. Chavan, Kevin J. Tracey, Aviv Regev, Frank C. Schroeder, Francis S. Lee, Conor Liston () and David Artis ()
Additional contact information
Coco Chu: Cornell University
Mitchell H. Murdock: Cornell University
Deqiang Jing: Cornell University
Tae Hyung Won: Cornell University
Hattie Chung: Broad Institute of MIT and Harvard
Adam M. Kressel: Northwell Health
Tea Tsaava: Northwell Health
Meghan E. Addorisio: Northwell Health
Gregory G. Putzel: Cornell University
Lei Zhou: Cornell University
Nicholas J. Bessman: Cornell University
Ruirong Yang: Cornell University
Saya Moriyama: Cornell University
Christopher N. Parkhurst: Cornell University
Anfei Li: Cornell University
Heidi C. Meyer: Cornell University
Fei Teng: Cornell University
Sangeeta S. Chavan: Northwell Health
Kevin J. Tracey: Northwell Health
Aviv Regev: Broad Institute of MIT and Harvard
Frank C. Schroeder: Cornell University
Francis S. Lee: Cornell University
Conor Liston: Cornell University
David Artis: Cornell University

Nature, 2019, vol. 574, issue 7779, 543-548

Abstract: Abstract Multicellular organisms have co-evolved with complex consortia of viruses, bacteria, fungi and parasites, collectively referred to as the microbiota1. In mammals, changes in the composition of the microbiota can influence many physiologic processes (including development, metabolism and immune cell function) and are associated with susceptibility to multiple diseases2. Alterations in the microbiota can also modulate host behaviours—such as social activity, stress, and anxiety-related responses—that are linked to diverse neuropsychiatric disorders3. However, the mechanisms by which the microbiota influence neuronal activity and host behaviour remain poorly defined. Here we show that manipulation of the microbiota in antibiotic-treated or germ-free adult mice results in significant deficits in fear extinction learning. Single-nucleus RNA sequencing of the medial prefrontal cortex of the brain revealed significant alterations in gene expression in excitatory neurons, glia and other cell types. Transcranial two-photon imaging showed that deficits in extinction learning after manipulation of the microbiota in adult mice were associated with defective learning-related remodelling of postsynaptic dendritic spines and reduced activity in cue-encoding neurons in the medial prefrontal cortex. In addition, selective re-establishment of the microbiota revealed a limited neonatal developmental window in which microbiota-derived signals can restore normal extinction learning in adulthood. Finally, unbiased metabolomic analysis identified four metabolites that were significantly downregulated in germ-free mice and have been reported to be related to neuropsychiatric disorders in humans and mouse models, suggesting that microbiota-derived compounds may directly affect brain function and behaviour. Together, these data indicate that fear extinction learning requires microbiota-derived signals both during early postnatal neurodevelopment and in adult mice, with implications for our understanding of how diet, infection, and lifestyle influence brain health and subsequent susceptibility to neuropsychiatric disorders.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41586-019-1644-y Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:574:y:2019:i:7779:d:10.1038_s41586-019-1644-y

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-019-1644-y

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().