Layer-specific input to medial prefrontal cortex is linked to stress susceptibility

Area of Science:

• Neuroscience
• Stress Research
• Synaptic Plasticity

Background:

• Stress response is vital for adaptation, but mechanisms of stress susceptibility are unclear.
• Chronic stress affects medial prefrontal cortex (mPFC) structure, but long-range synaptic impacts are unknown.

Purpose of the Study:

• Investigate how stress affects synapses from ventral hippocampus (VH), basolateral amygdala (BLA), and ventral tegmental area (VTA) to the mPFC in different stress phenotypes.
• Determine if stress susceptibility leads to specific synaptic reorganization patterns.

Main Methods:

• Labeled synapses from VH, BLA, and VTA to male mouse mPFC using eGRASP.
• Acquired 3D images of mPFC and segmented dendrites and synapses.
• Analyzed synapse abundance, spatial organization, and proximity in stress-naïve, resilient, and susceptible mice.

Main Results:

• Synapse organization in superficial layers (II/III) showed similar changes in resilient and susceptible mice compared to controls.
• In deep layers (Vb, VI), stress susceptible mice exhibited increased BLA-mPFC and decreased VH-mPFC synapses.
• Synaptic inputs to deep mPFC layers became disorganized in stress susceptible mice, with increased multi-region innervation.

Conclusions:

• Stress phenotypes differentially reorganize long-range synaptic inputs to the mPFC in an afferent- and lamina-specific manner.
• These findings suggest distinct roles for VH, BLA, and VTA projections in mediating stress responses and susceptibility.