Distinct orbitofrontal circuits with dorsal and ventral CA1 differentially regulate spatial memory and emotional...

Area of Science:

• Neuroscience
• Cognitive Neuroscience
• Systems Neuroscience

Background:

• The orbitofrontal cortex (OFC) and hippocampus are crucial for cognitive and affective functions.
• The specific circuit architecture linking the OFC with dorsal CA1 (dCA1) and ventral CA1 (vCA1) is not well understood.

Purpose of the Study:

• To investigate the anatomical and functional organization of OFC-hippocampal connectivity in mice.
• To elucidate how distinct OFC-CA1 circuits regulate spatial memory and affect-related behaviors.

Main Methods:

• Combined viral circuit tracing and targeted neuronal ablation in mice.
• Mapped direct and polysynaptic pathways using dual viral tracing.
• Assessed behavioral functions via spatial memory and emotion-related tests.

Main Results:

• Identified a unidirectional OFC→claustrum→dCA1 pathway, selectively impairing spatial memory upon disconnection.
• Revealed distinct vCA1 connectivity to OFC via multiple indirect routes, with disconnection inducing anxiety- and depression-like behaviors.
• No reciprocal dCA1→OFC or direct OFC→vCA1 projections were found.

Conclusions:

• OFC interacts with dCA1 and vCA1 through anatomically separate circuits.
• These distinct circuits have dissociable roles in regulating spatial memory and affect.
• Provides circuit-level insights into OFC-hippocampal functional organization.