The optokinetic reflex as a tool for quantitative analyses of nervous system function in mice: application to genetic and drug-induced variation.
The optokinetic reflex (OKR), which serves to stabilize a moving image on the retina, is a behavioral response that has many favorable attributes as a test of CNS function. The OKR requires no training, assesses the function of diverse CNS circuits, can be induced repeatedly with minimal fatigue or adaptation, and produces an electronic record that is readily and objectively quantifiable. We describe a new type of OKR test apparatus in which computer-controlled visual stimuli and streamlined data analysis facilitate a relatively high throughput behavioral assay. We used this apparatus, in conjunction with infrared imaging, to quantify basic OKR stimulus-response characteristics for C57BL/6J and 129/SvEv mouse strains and for genetically engineered lines lacking one or more photoreceptor systems or with an alteration in cone spectral sensitivity. A second generation (F2) cross shows that the characteristic difference in OKR frequency between C57BL/6J and 129/SvEv is inherited as a polygenic trait. Finally, we demonstrate the sensitivity and high temporal resolution of the OKR for quantitative analysis of CNS drug action. These experiments show that the mouse OKR is well suited for neurologic testing in the context of drug discovery and large-scale phenotyping programs.
Cahill
Hugh
H
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Nathans
Jeremy
J
D000818:Animals; D002491:Central Nervous System Agents / Q000494:pharmacology*; D014644:Genetic Variation / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D020412:Multifactorial Inheritance / Q000187:drug effects; D009424:Nervous System Physiological Phenomena / Q000187:drug effects*; D017120:Nystagmus, Optokinetic / Q000502:physiology*; D010775:Photic Stimulation; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects; D012018:Reflex / Q000187:drug effects*; D013997:Time Factors
D002491:Central Nervous System Agents; D007649:Ketamine