ETD

• aversion
• chemogenetics
• lateral habenula
• locus coeruleus
• neuroscience
• optogenetics
• stress
• tracing

Stress is a critical risk factor for both somatic and neuropsychiatric diseases, yet the precise circuitry behind maladaptive responses to chronic stress remains incompletely understood.
Our understanding of the physiological and biological mechanisms of stress is crucial to develop effective and structured pharmacological solutions to prevent or reduce its symptomatology.
The main aim of this work is to expand our understanding of the neurophysiology underlying maladaptive stress responses through a multi-level analysis of a cerebral circuit whose main nodes are lateral habenula (LHb), often considered the brain aversion centre, and the Locus coeruleus (LC), one of the major noradrenergic hubs in the central nervous system (CNS).
We used viral tracing, electrophysiology, behavioural studies, and molecular techniques to identify a functional connection between LHb neurons and a recently identified population of GABAergic neurons in the LC. We also confirmed stress-relevant endocrine and behavioural effects of this ensemble in mice using chemogenetic manipulations.

These findings advance our understanding of LC related brain circuits contributing to physiological and behavioural adaptations to stress and identify a promising target for pharmacological targeting to alleviate stress-related maladaptive behaviours.