title: Impairment of the anterior thalamic head direction cell network following administration of the NMDA antagonist MK-801.
abstract: Head direction (HD) cells, found in the rodent Papez circuit, are thought to form the neural circuitry responsible for directional orientation. Because NMDA transmission has been implicated in spatial tasks requiring directional orientation, we sought to determine if the NMDA antagonist dizocilpine (MK-801) would disrupt the directional signal carried by the HD network. Anterior thalamic HD cells were isolated in female Long-Evans rats and initially monitored for baseline directional activity while the animals foraged in a familiar enclosure. The animals were then administered MK-801 at a dose of .05 mg/kg or 0.1 mg/kg, or isotonic saline, and cells were re-examined for changes in directional specificity and landmark control. While the cells showed no changes in directional specificity and landmark control following administration of saline or the lower dose of MK-801, the higher dose of MK-801 caused a dramatic attenuation of the directional signal, characterized by decreases in peak firing rates, signal to noise, and directional information content. While the greatly attenuated directional specificity of cells in the high dose condition usually remained stable relative to the landmarks within the recording enclosure, a few cells in this condition exhibited unstable preferred directions within and between recording sessions. Our results are discussed relative to the possibility that the findings explain the effects of MK-801 on the acquisition and performance of spatial tasks.
authors.affiliation: California State University Sacramento USA.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Housh
authors.affiliation: California State University Sacramento USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Berkowitz
authors.affiliation: California State University Sacramento USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Ybarra
authors.affiliation: California State University Sacramento USA.
authors.forename: Esther U
authors.initials: EU
authors.lastname: Kim
authors.affiliation: California State University Sacramento USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Lee
authors.affiliation: California State University Sacramento USA. Electronic address: calton@csus.edu.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Calton
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D016291:Dizocilpine Maleate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005260:Female; D009068:Movement / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D009949:Orientation / Q000187:drug effects*; D010468:Perceptual Disorders / Q000139:chemically induced*; D051381:Rats; D020318:Rats, Long-Evans; D013037:Spatial Behavior / Q000187:drug effects; D013788:Thalamus / Q000166:cytology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate
keywords: Dizocilpine; N-methyl-D-aspartate; Navigation; Place cells; Rat; Spatial orientation