The Royal College of Surgeons (RCS) rat is the first animal known to show inherited retinal degeneration. A retinal pigment epithelial cell defect causes a progressive loss of rod and cone photoreceptors, which occurs primarily in the first few months of life. Using this characteristic, the various recovery studies including the graft study and development of artificial vision systems have been conducted. Moreover, the visual ability of RCS rat has been examined by recording the visual responses in the superior colliculus, showing the temporal loss of the visual responses. However, the visual ability in the freely behaving RCS rat have not been psychophysically measured yet because their visual function is lost before they learn the visual stimulus detection task which generally takes a long-term training period. Therefore, the temporal changes in behavioral visual sensitivity of RCS rat remain unknown.
To overcome this problem, we developed an efficient and stable training system for the two-alternative forced-choice visual cue detection task (2AFC-VCDT) for freely behaving rodents (using Long-Evans rats). To facilitate the task learning, we introduced a spout-lever as the operandum and a three-step training program with four ingenuities: 1) a salient stimulus to draw passive attention, 2) a reward-guaranteed trial to keep motivation, 3) a behavior-corrective trial, and 4) switching from a reward-guaranteed trial to a non-guaranteed one to correct behavioral patterns. Our new training system realizes one-week completion of the whole learning process, during which all rats were able to learn effortlessly the association between 1) lever-manipulation and reward and 2) visual stimulus and reward in a step-by-step manner. Thus, our new system provides an effective and stable training method for the 2AFC-VCDT. Using this method, we trained the RCS rat before development of retinitis pigmentosa at 3 wk of age, and successfully measured their visual contrast sensitivity which was declined over the three months of life.
This work was supported by KAKENHI, 26780415 and Grant for Tateisi Science and Technology Foundation to S. Soma.