Implicit learning in a serial choice visual discrimination task in the operant 9-hole box by intact and striatal lesioned mice

Abstract

Within a broader programme developing murine models of Huntington's disease (HD), we have sought to develop a test of implicit learning for the mouse. Mice were trained in a novel serial visual discrimination task in the ‘9-hole box’ operant test apparatus, followed by retesting after either bilateral quinolinic acid striatal lesions or sham lesions. In the task, each trial involves two sequential responses: an initial light stimulus is presented randomly in one of five holes, to which a nose-poke response results in the first light being extinguished and a second light is illuminated in a different hole. Response to the second light results in food reward, followed by a brief interval before the next trial. When the first light was in one of three of the five holes, the location of the second light was unpredictable in any of the remaining four holes; by contrast, if the first light occurred in one of the other two of the five holes, then the location of the second light was entirely predictable, being the hole two steps to the left or to the right, respectively. Reaction times and accuracy of responding were recorded to both stimuli. The mice learned the task with a degree of accuracy, and they demonstrated clear implicit learning, as measured by increased accuracy and reduced latency to respond to the presentation of the predictable stimulus. Striatal lesions disrupted performance, reducing accuracy for both the first and second stimuli and increasing response latencies for the second stimuli. The decrease in accuracy by the lesioned animals was accompanied by increases in perseverative nose-poking and inappropriate magazine entries throughout the trials, but the lesioned mice still showed a similar benefit (albeit, against a lower baseline of performance) from the implicit knowledge provided on predictable trials. The data validates the task as a sensitive probe for determining implicit learning deficits in the mouse, and suggests that the consequences of striatal lesions, while disrupting performance of skilled stimulus-response habits, are not selective to the process underlying implicit learning.