Key result
Silencing central amygdala neurons during acute sepsis prevents anxiety behaviors in mice.
Why the study?
Post-sepsis syndrome includes long-term psychiatric disorders such as persistent anxiety and PTSD, but their neurobiological mechanisms remain unknown.
Specific inhibition of brain anxiety and fear circuits during the acute phase of sepsis constitutes a potential preventive approach to preclude post-infection psychiatric outcomes.
May prevent post-sepsis anxiety via amygdala targeting in mice; hypothesis-generating and untested in humans.
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.
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Bourhy et al. (2021) studied Sepsis and post-sepsis syndrome. Transient silencing of central amygdala neurons (viral pharmacogenetic approach or levetiracetam) was evaluated on Development of anxiety-related behaviours. Transient silencing of specific central amygdala neurons during the acute phase of sepsis, using a viral pharmacogenetic approach or levetiracetam, prevented the development of anxiety-related behaviours in mice.
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