Abstract
Purpose:
Visual acuity (VA) requires the entire visual system including focus, neural processing, and integration. VA is the primary endpoint for evaluating potential toxicity of therapies as well as treatment efficacy for vision-threatening diseases, but VA is challenging to measure in laboratory animals. Thus, surrogate measures of vision like ERG’s are used to evaluate retinal function and VEPs to measure brain responses to light. The optokinetic response, a reflexive reaction to a moving stimulus, fails to evaluate full visual system integration and measurement requires significant operator involvement. Behavioral conditioning incorporates the entire visual system by training subjects to respond to visual stimuli. Such a system typically requires a behavioral psychologist which is a barrier to widespread use. We are developing an operant conditioning system with pre-established protocols for training rodents to a visual task and evaluating VA without the need for highly trained technicians.
Methods:
Each system included an LCD monitor, two retractable levers and a food pellet dispenser. Rats were trained to deferentially respond on levers to a 0.04 c/d sine wave grating or a gray stimuli. Once trained to identify the target with 80% accuracy over 8 sessions, the spatial density was varied step-wise until accuracy was reduced to chance. Progress of the animals through each training and testing phase was controlled using custom software such that little decision making was required by the technician.
Results:
CD rats showed no signs of discrimination acquisition and their training session was suspended. Long Evans (LE) rats required greater than 50 training sessions to reach 80% accuracy, but showed indications of acquisition after 30 sessions. Visual function threshold for LE rats was 0.8 c/d and within the normal range of published data.
Conclusions:
Operant conditioning provided environmental control and allowed the automation of complex training and testing protocols with limited technician involvement. Hardware modifications to reduce the training duration to the initial visual task and additional behavioral schedules will be investigated. Additional options such as sharing of animal progression between chambers will allow flexibility of testing and inclusion of a chip reader may reduce potential ID errors. This system will provide a reliable, high throughput, low labor-intensive platform to measure VA in rodents.
Keywords: 754 visual acuity •
503 drug toxicity/drug effects •
753 vision and action