Place cell firing cannot support navigation without intact septal circuits

Hippocampus. 2020 Mar;30(3):175-191. doi: 10.1002/hipo.23136. Epub 2019 Jul 13.

Abstract

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.

Keywords: hippocampus; medial septum; place cells; spatial navigation; theta oscillations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Anesthetics, Local / pharmacology
  • Animals
  • GABA-A Receptor Agonists / pharmacology
  • GABA-A Receptor Antagonists / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Male
  • Muscimol / pharmacology
  • Place Cells / drug effects
  • Place Cells / physiology*
  • Pyridazines / pharmacology
  • Rats
  • Rats, Long-Evans
  • Septum of Brain / drug effects
  • Septum of Brain / physiology*
  • Spatial Navigation / drug effects
  • Spatial Navigation / physiology*
  • Tetracaine / pharmacology

Substances

  • Anesthetics, Local
  • GABA-A Receptor Agonists
  • GABA-A Receptor Antagonists
  • Pyridazines
  • Tetracaine
  • Muscimol
  • gabazine