Chronic Social Defeat Stress Induces Pathway-Specific Adaptations at Lateral Habenula Neuronal Outputs.

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Stress and Mood Disorders

Background:

• The lateral habenula (LHb) is a key brain region implicated in depression, often showing hyperactivity.
• Understanding synaptic changes in LHb outputs is crucial for elucidating depression mechanisms.

Purpose of the Study:

• To investigate synaptic transmission alterations in major LHb efferent circuits after chronic social defeat stress (CSDS).
• To identify circuit-specific synaptic adaptations in response to chronic stress.

Main Methods:

• Optogenetics, retrograde tracing, and ex vivo whole-cell patch-clamp electrophysiology.
• Analysis of synaptic transmission at LHb outputs to the dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and rostromedial tegmental nucleus (RMTg) in male mice subjected to CSDS.

Main Results:

• CSDS induced postsynaptic potentiation in DRN-projecting neurons and postsynaptic depression in VTA-projecting neurons.
• CSDS altered presynaptic transmission at LHb terminals in the RMTg in both susceptible and resilient mice.
• VTA-projecting LHb neurons showed decreased spontaneous activity; RMTg-projecting LHb neurons exhibited altered excitatory-inhibitory balance.

Conclusions:

• Chronic social stress induces distinct, circuit-specific synaptic adaptations in LHb efferent pathways.
• These findings highlight potential synaptic mechanisms underlying stress-induced depressive-like states.