A long list visuo-spatial sequential learning in mice.

Sequential learning has been extensively studied in humans using the serial reaction time (SRT) paradigm, and has contributed significantly to the description of the neurobiological processes and substrates underlying different memory systems. More precisely, patients with basal ganglia, but not medial temporal lobe pathology exhibit selective deficits in this task, qualified as implicit learning, since this learning occurs without any conscious awareness of the subjects. While, the construction of transgenic mouse models of human neurological diseases has created a great need for developing mouse analogs of this or other types of human memory tasks, only a few studies exist in rodents, and more specifically in mice. The present study is aimed at examining a SRT protocol for mice using our new operant chamber designed to be polyvalent for different experimental conditions and uses. We provide data for learning by normal C57BL/6 mice of a repeating sequence of 12 nose poke responses, first, via the observation of increases in reaction times when repeated sequence is replaced by random sequence, and, second, by analysis of behavior during transfer trials in which one sequential element is discretely replaced by a new item. The potential of our protocol for dissecting the different neural systems of learning and memory is discussed as well as its usefulness for the validation of transgenic mouse models of human neurodegenerative diseases such as Huntington's disease and Alzheimer's disease.