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

Institut Pasteur. Université Paris Cité. Laboratory for Experimental Neuropathology. Paris, France / Institut Pasteur. Université Paris Cité. CNRS UMR 3571. Perception and Memory Unit. Paris, France / Université Paris Cité. Collège doctoral. Paris, France.
Institut Pasteur. Université Paris Cité. Laboratory for Experimental Neuropathology. Paris, France / Université Paris Cité. Collège doctoral. Paris, France / GHU Paris Psychiatrie Neurosciences. Service hospitalo-universitaire de Neuro-anesthésie réanimation. Paris, France.
Institut Pasteur. Université Paris Cité. Laboratory for Experimental Neuropathology. Paris, France / University of São Paulo. School of Dentistry of Ribeirão Preto. Department of Basic and Oral Biology. Ribeirão Preto, SP, Brazil.
Institut Pasteur. Université Paris Cité. CNRS UMR 3571. Perception and Memory Unit. Paris, France.
Institut Pasteur. Université Paris Cité. CNRS UMR 3571. Perception and Memory Unit. Paris, France.
Institut Pasteur. Université Paris Cité. CNRS UMR 3571. Perception and Memory Unit. Paris, France.
Institut Pasteur. Université Paris Cité. CNRS UMR 3571. Perception and Memory Unit. Paris, France / Institut Pasteur. Université Paris Cité. Microenvironment and Immunity Unit. Paris, France.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.
Institut Pasteur. Université Paris Cité. Laboratory for Experimental Neuropathology. Paris, France / GHU Paris Psychiatrie Neurosciences. Service hospitalo-universitaire de Neuropathologie. Paris, France.
Institut Pasteur. Université Paris Cité. CNRS UMR 3571. Perception and Memory Unit. Paris, France.
HU Paris Psychiatrie Neurosciences. Service hospitalo-universitaire de Neuro-anesthésie réanimation. Paris, France / Institut de Psychiatrie et Neurosciences de Paris. INSERM UMR 1266. Paris, France.
Institut Pasteur. Université Paris Cité. CNRS UMR 3571. Perception and Memory Unit. Paris, France.

Abstract

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.

Keywords

Cecal ligation and puncture
Fear conditioning
Neuro-immune interactions
Neuroinflammation
Optogenetic

Publisher

Oxford

Citation

BOURHY, Lena et al. Silencing of amygdala circuits during sepsis prevents the development of anxiety-related behaviours. Brain: a Journal of Neurology, v. 145, n. 4, p. 1391-1409, 2022.

DOI

10.1093/brain/awab475

ISSN

0006-8950

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/55222

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Open access

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