An entorhinal-visual cortical circuit regulates depression-like behaviors

Area of Science:

• Neuroscience
• Circuitopathy
• Depression Research

Background:

• Major depressive disorder is increasingly understood as a circuitopathy.
• The hippocampal-entorhinal network is crucial for depression regulation.
• The entorhinal-visual cortical pathway's role in depression is largely unknown.

Purpose of the Study:

• To investigate the role of the entorhinal-visual cortical pathway in depression.
• To identify the specific neural circuits and mechanisms involved.
• To explore the potential of this pathway as a therapeutic target for major depressive disorder.

Main Methods:

• Analysis of brain-wide projections and retrograde tracing to identify unique neuronal populations.
• Immunostaining (c-Fos) to assess neuronal activity under stress.
• Chemogenetics and optogenetics to manipulate neuronal activity.
• Fiber photometry to record neural activity during behavioral tasks.

Main Results:

• A specific cortical circuit (Ent→V2M) linking entorhinal cortex layer Va neurons to the secondary visual cortex was identified.
• Activity in Ent→V2M neurons decreased under chronic social defeat stress (CSDS).
• Inactivation of this circuit induced depression-like behaviors, while activation rapidly ameliorated them.

Conclusions:

• The Ent→V2M circuit bidirectionally regulates depression-like behaviors.
• This circuit represents a novel and promising target for major depressive disorder treatment.
• Understanding this pathway offers new insights into the neurobiology of depression.