Prefrontal-Bed Nucleus Circuit Modulation of a Passive Coping Response Set

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Neuroendocrinology

Background:

• Understanding the neural circuits that organize complex stress responses is a key challenge in neuroscience.
• The medial prefrontal cortex (mPFC) processes cognitive and affective information, while the anteroventral bed nuclei of the stria terminalis (avBST) integrates homeostatic signals.
• The mPFC's influence over the avBST is hypothesized to orchestrate multiple features of adaptive stress responses.

Purpose of the Study:

• To investigate the role of the mPFC's influence over the avBST in organizing adaptive stress responses.
• To determine if the prelimbic region of the mPFC can modulate endocrine and behavioral stress outputs via the avBST.

Main Methods:

• Optogenetic inhibition and photostimulation of the prelimbic mPFC to avBST pathway in male rats.
• Assessment of immobility (a measure of passive coping) and hypothalamo-pituitary-adrenal (HPA) axis activity during tail suspension.
• Anatomical tracing to identify projections from the prelimbic cortex to avBST and downstream effector neurons.
• Behavioral testing using the shock-probe defensive burying test to assess active and passive coping strategies.

Main Results:

• Inhibition of the prelimbic mPFC input to avBST increased immobility and HPA output during stress.
• Photostimulation of this pathway decreased immobility during the same stressor.
• Anatomical studies confirmed projections from the prelimbic cortex to avBST neurons, which then project to HPA effector nuclei and midbrain periaqueductal gray.
• Pathway stimulation/inhibition selectively altered passive coping behaviors (defensive burying) without affecting active coping.

Conclusions:

• The prelimbic mPFC to avBST pathway is a critical neural substrate for coordinating a 'response set' during threat exposure.
• This circuit selectively gates passive coping behaviors and restrains neuroendocrine activation, optimizing adaptation to stressors.
• Disruptions in this pathway may contribute to maladaptive responses seen in stress-related psychiatric disorders.