Homeostatic scaling ensures behavioural stability during corticosterone negative feedback

Area of Science:

• Neuroscience
• Stress Physiology
• Behavioral Biology

Background:

• Chronic stress and elevated corticosteroids (CORT) impact physiological and behavioral responses.
• The effect of prolonged CORT exposure on survival behaviors during acute stress is not fully understood.
• Corticotropin-releasing hormone neurons (CRH) in the paraventricular nucleus of the hypothalamus (PVN) are key regulators of stress responses.

Purpose of the Study:

• To investigate the impact of short-term and long-term CORT exposure on innate defensive behaviors.
• To elucidate the neural mechanisms underlying behavioral adaptation to chronic stress.
• To determine if survival-promoting behaviors are maintained despite suppressed CRH neuron activity.

Main Methods:

• Aerial predator threat model in rodents.
• In vivo calcium imaging and whole-cell electrophysiology.
• Chemogenetics and computational modeling.

Main Results:

• Short-term CORT exposure blunts CRH neuron activity and defensive behaviors via negative feedback.
• Long-term CORT exposure leads to behavioral recovery despite persistent low CRH neuron activity.
• Homeostatic scaling of glutamate synapses in CRH neurons overcomes CORT inhibition, preserving system output.

Conclusions:

• Homeostatic synaptic scaling is a crucial local adaptive mechanism in the brain.
• This scaling preserves the function of essential survival circuits during chronic stress.
• The brain demonstrates resilience by adapting neural circuits to maintain vital defensive responses.