The ventral hippocampus and the lateral septum work in tandem to regulate rats' open-arm exploration in the elevated plus-maze.

Lesions or pharmacological inhibition of the ventral hippocampus or the lateral septum suppress rats' defensive responses in various rat models of anxiety. Although these two structures are extensively connected, it was not clear whether they regulate anxiety in a parallel (independent) or serial (integrated) fashion. In Experiment 1, bilateral infusions of the GABA-A receptor agonist muscimol (5 ng/side) into the lateral septum increased rats' open-arm exploration in the elevated plus-maze test, whereas unilateral infusions of muscimol did not. Similar anxiolytic-like effects were observed in Experiment 2, following bilateral infusions of muscimol (500 ng/side) into the ventral hippocampus. In Experiment 3, we confirmed that unilateral infusions of muscimol into either the lateral septum (5 ng) or the ventral hippocampus (500 ng) did not alter rats' normal open-arm avoidance. Importantly, dramatic increases in open-arm exploration were evident when muscimol was co-infused into one side of the lateral septum (5 ng) and the contralateral ventral hippocampus (500 ng). By contrast, open-arm exploration was not altered when these same doses of muscimol were co-infused into one side of the lateral septum and the ipsilateral ventral hippocampus. These results support the contention that the ventral hippocampus and the lateral septum regulate rats' open-arm exploration in a serial fashion, and that this involves ipsilateral projections from the former to the latter site.