Silencing of amygdala circuits during sepsis prevents the development of anxiety-related behaviours

Sepsis is a life-threatening condition induced by a deregulated host response to severe infection. Post-sepsis syndrome includes long-term psychiatric disorders, such as persistent anxiety and post-traumatic stress disorder, whose neurobiological mechanisms remain unknown. Using a reference mouse mo...

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Bibliographic Details
Published in:	Brain (London, England : 1878) Vol. 145; no. 4; pp. 1391 - 1409
Main Authors:	Bourhy, Lena, Mazeraud, Aurélien, Costa, Luis H A, Levy, Jarod, Rei, Damien, Hecquet, Estéban, Gabanyi, Ilana, Bozza, Fernando A, Chrétien, Fabrice, Lledo, Pierre-Marie, Sharshar, Tarek, Lepousez, Gabriel
Format:	Journal Article
Language:	English
Published:	England Oxford University Press 24-05-2022
Subjects:	Animals Anxiety Anxiety Disorders Central Amygdaloid Nucleus Cognitive science Fear - physiology Humans Mice Neuroscience Original Sepsis - complications fear conditioning neuroinflammation optogenetic neuro-immune interactions cecal ligation and puncture
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Summary:	Sepsis is a life-threatening condition induced by a deregulated host response to severe infection. Post-sepsis syndrome includes long-term psychiatric disorders, such as persistent anxiety and post-traumatic stress disorder, whose neurobiological mechanisms remain unknown. Using a reference mouse model of sepsis, we showed that mice that recovered from sepsis further developed anxiety-related behaviours associated with an exaggerated fear memory. In the brain, sepsis induced an acute pathological activation of a specific neuronal population of the central nucleus of the amygdala, which projects to the ventral bed nucleus of the stria terminalis. Using viral-genetic circuit tracing and in vivo calcium imaging, we observed that sepsis induced persistent changes in the connectivity matrix and in the responsiveness of these central amygdala neurons projecting to the ventral bed nucleus of the stria terminalis. The transient and targeted silencing of this subpopulation only during the acute phase of sepsis with a viral pharmacogenetic approach, or with the anti-epileptic and neuroprotective drug levetiracetam, prevented the subsequent development of anxiety-related behaviours. Specific inhibition of brain anxiety and fear circuits during the sepsis acute phase constitutes a preventive approach to preclude the post-infection psychiatric outcomes.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC9128826 These authors contributed equally to this work.
ISSN:	0006-8950 1460-2156
DOI:	10.1093/brain/awab475