Orexinergic neurons modulate stress coping responses in mice

Area of Science:

• Neuroscience
• Behavioral Science
• Psychiatry

Background:

• Stress is a major trigger for depression, but individual resilience varies.
• Factors influencing stress susceptibility and resilience are not fully understood.
• Orexin neurons regulate stress-induced arousal.

Purpose of the Study:

• To investigate the role of orexin-expressing neurons in regulating stress resilience in male mice.
• To explore how activating orexinergic neurons affects behavioral responses to stress.

Main Methods:

• Utilized the learned helplessness test (LHT) and escape test in male mice.
• Measured c-fos expression to assess neuronal activity.
• Employed optogenetic stimulation of orexinergic neurons and their projections.

Main Results:

• Orexin neuron activation induced resilience in stress-susceptible mice in the LHT.
• Activating orexinergic neurons during stress exposure did not alter resilience in the escape test.
• Orexinergic projections to the nucleus accumbens reduced anxiety but did not confer LHT resilience alone.

Conclusions:

• Orexin neurons play a significant role in modulating stress resilience.
• Orexinergic projections to multiple brain regions collectively regulate diverse stress-related behaviors.
• These findings offer insights into potential therapeutic targets for stress and depression.