Parallel ventral hippocampus-lateral septum pathways differentially regulate approach-avoidance conflict.

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Systems Neuroscience

Background:

• Adaptive behavior requires resolving approach-avoidance conflicts.
• The ventral hippocampus (vHPC), specifically subfields CA3 (vCA3) and CA1 (vCA1), differentially regulates avoidance and approach behaviors.
• The neural circuits underlying this subfield-specific regulation remain largely unknown.

Purpose of the Study:

• To elucidate the distinct neural pathways from vCA3 and vCA1 to the lateral septum (LS) that mediate divergent control over approach-avoidance behavior.
• To investigate the role of these pathways in regulating responses to motivational conflict and environmental uncertainty.

Main Methods:

• Utilized chemogenetics in Long-Evans rats to selectively inhibit specific vHPC-LS pathways.
• Assessed behavioral responses, including approach and exploration, during conflict-eliciting tasks and environmental uncertainty.

Main Results:

• Inhibition of the vCA3-LS caudodorsal (cd) pathway potentiated approach to conflict stimuli and reduced hesitation in exploring food during uncertainty.
• Inhibition of the vCA1-LS rostroventral (rv) pathway led to non-specific potentiation of approach and delayed food exploration initiation.
• Demonstrated distinct roles for vCA3-LScd and vCA1-LSrv pathways in modulating specific aspects of motivated behavior.

Conclusions:

• The vHPC exerts differential control over behavioral systems through distinct projections to the LS.
• The LS acts as a critical relay, sending inhibitory projections to downstream motivational centers.
• These findings reveal a circuit-level mechanism for how the vHPC regulates adaptive decision-making in the face of conflict and uncertainty.