Measures of pupillary and oculomotor function are exquisitely sensitive to modulation of the central nervous system (CNS) by drugs of abuse and CNS pathology in nonhuman primate (NHP) models of human diseases. However, techniques to study pupillary and oculomotor function in NHPs traditionally require invasive procedures including surgical implantation and/or restraint of the animals in specialized chairs. These techniques allow very powerful analyses of the visual system, but limit the number of researchers that can utilize eye-tracking in NHPs. This proposal will combine state-of-the-art, computerized video-based eye-tracking equipment with novel behavioral methods to develop a method for pupillometry and gaze-tracking in NHPs in their home cage.
Specific Aim 1 is to develop a system that attaches to a nonhuman primate home cage and allows computer-based video recording of the nonhuman primate eye while the animal is awake and unrestrained. Measures to be recorded include estimates of pupil size and direction of the monkey's gaze.
Specific Aim 2 is to develop a procedure for determination of pupillary light reflex. Determination of pupillary light reflex will be validated by measuring the effects of morphine in rhesus monkeys and baboons. Pupillometry will be measured in baboons to test the training methods and equipment in an additional nonhuman primate species.
Specific Aim 3 is to develop a system to measure gaze direction while rhesus monkeys perform a visual smooth pursuit task. Sensitivity of the smooth pursuit task will be validated by testing the effects of diazepam on oculomotor performance of rhesus monkeys.
Specific Aim 4 is to develop a test of recognition memory based on relative gaze times to two stimuli, the Visual Paired Comparisons test in rhesus monkeys. Administration of diazepam will test for the sensitivity of the paradigm to the amnesic effects of benzodiazepines. Measures of pupillary dilation will be included to address whether dilation due to cognitive load is evident in this paradigm. Home cage procedures will enable more researchers to eye-tracking techniques and reduce the technical difficulty of doing so. Home cage procedures will also reduce the stress to the NHP subjects inherent in restraint-based methods. The techniques presented here will be most attractive to non-traditional users of eye-based measures such as pharmacologists, neurotoxicologists and behavioral psychologists. ? ? ? ?
