Place cell firing cannot support navigation without intact septal circuits

Though it has been known for over half a century that interference with the normal activity of septohippocampal neurons can abolish hippocampal theta rhythmicity, a definitive answer to the question of its function has remained elusive. To clarify the role of septal circuits and theta in location specific activity of place cells and spatial behavior, three drugs were delivered to the medial septum of rats: tetracaine, a local anesthetic; muscimol, a GABA-A agonist; and gabazine, a GABA-A antagonist. All three drugs disrupted normal oscillatory activity in the hippocampus. However, tetracaine and muscimol both reduced spatial firing and interfered with the rat’s ability to navigate to a hidden goal. After gabazine, location specific firing was preserved in the absence of theta, but rats were unable to accurately locate the hidden goal. These results indicate that theta is unnecessary for location specific firing of hippocampal cells, and that place cell activity cannot support accurate navigation when septal circuits are disrupted.