Stress History Modulates CRF Neurons to Establish Resilience

Area of Science:

• Neuroscience
• Psychiatry
• Stress Research

Background:

• Cumulative stress is a major risk factor for major depressive disorder (MDD).
• Not all individuals exposed to chronic stress develop MDD, indicating underlying resilience mechanisms.
• The point and mechanism by which resilience emerges remain unclear.

Purpose of the Study:

• To investigate the neurobiological mechanisms underlying resilience to chronic stress.
• To identify the critical period and neural adaptations associated with developing resilience.
• To examine the role of the bed nucleus of the stria terminalis oval nucleus (BNSTov) in stress resilience.

Main Methods:

• Utilized a 10-day repeated social defeat stress model (RSDS) in mice.
• Employed cell-type selective electrophysiology, chemogenetics, optogenetics, and fiber photometry.
• Conducted RNA quantification to assess neuroadaptation in the BNSTov.

Main Results:

• A critical period between days 7 and 10 of daily defeats marked the divergence between resilient and susceptible mice.
• Corticotropin-releasing factor (CRF)+ neurons in the BNSTov showed sustained increased firing rates in resilient mice, but not susceptible mice.
• This neurophysiological adaptation was self-sustaining after 7 stress exposures, highlighting stress history's role.

Conclusions:

• Resilience involves stress-provoked activation, not inhibition, of CRF+ neurons in the BNSTov.
• This activation establishes a novel pathway for persisting in the face of adversity.
• The development of resilience is dependent on prior stress history.