Combined Blockade of Serotonergic and Muscarinic Transmission Disrupts the Anterior Thalamic Head Direction Signal

• Published in: Behavioral neuroscience 2008-12, Vol.122 (6), p.1226-1235
• Main Authors: Sandoval, Kate, McDaniel, Kathrine M, Murawski, Nathen J, Doerr, Celeste E, Calton, Jeffrey L
• Format: Article
• Language: English
• Subjects: Acetylcholine; Action Potentials - drug effects; Action Potentials - physiology; Animal; Animal Migratory Behavior; Animals; Antagonist drugs; Anterior Thalamic Nuclei - cytology; Anterior Thalamic Nuclei - drug effects; Anterior Thalamic Nuclei - physiology; Behavior, Animal - drug effects; Behavioral psychophysiology; Biological and medical sciences; Brain; Cholinergic Agents - metabolism; Drug Combinations; Female; Fundamental and applied biological sciences. Psychology; Head Movements - drug effects; Head Movements - physiology; Male; Methiothepin - pharmacology; Motor Activity - drug effects; Muscarinic Antagonists - pharmacology; N-Methylscopolamine - pharmacology; Neurons; Neurons - drug effects; Neurons - physiology; Neurosciences; Neurotransmitters; Orientation - drug effects; Orientation - physiology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Long-Evans; Rodents; Serotonin; Serotonin - metabolism; Serotonin Antagonists - pharmacology; Space Perception - drug effects; Space Perception - physiology; Spatial Orientation (Perception); Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Theta Rhythm
• ISSN: 0735-7044; 1939-0084
• DOI: 10.1037/a0013138

Head direction (HD) cells have been speculated to be part of a network mediating navigational behavior. Previous work has shown that combined administration of serotonergic and muscarinic antagonists eliminates hippocampal theta activity and produces navigational deficits more severe than blockade of either neurotransmitter system alone. The authors sought to assess this effect on the directional characteristics of HD cells. HD cells were recorded from the anterior dorsal thalamus of Long-Evans rats before and after administration of the serotonergic antagonist methiothepin, the muscarinic antagonist scopolamine, both drugs, or saline. Combined drug administration produced HD cells with preferred directions that drifted within recording sessions. In addition, cells showed shifts in the preferred directions at the start of a session relative to the position of the major landmarks, suggesting that combined drug administration led to deficits in landmark control of the HD system. Single drug exposures to methiothepin or scopolamine did not noticeably affect the directional characteristics of HD cells. This finding that navigation-impairing drugs can disrupt the HD signal provides further evidence that this network plays an important role in navigational behavior.