Abnormal strategies during visual discrimination reversal learning in ephrin-A2−/− mice

Eph receptors and ephrins are involved in establishing topographic connectivity in primary sensory brain regions, but also in higher order structures including the cortex and hippocampus. Ephrin-A2−/− mice have abnormal topography in the primary visual system but have normal visual and learning performance on a simple visual discrimination task. Here we use signal detection theory to analyse learning behaviour of these mice. Wild-type (WT) and ephrin-A2−/− (KO) mice performed equally well in a two-stimulus visual discrimination task, with similar learning rates and response latencies. However, during reversal learning, when the rewarded stimulus was switched, the two genotypes exhibited differences in response strategies: while WTs favoured a win-stay strategy, KOs remained relatively neutral. KOs also exhibited a stronger lateralization bias in the initial stages of learning, choosing the same arm of the maze with high probability. In addition, use of a Bayesian “optimal observer” revealed that compared to WT, KO mice adapted their decisions less rapidly to a change in stimulus-reward relationship. We suggest that the misexpression of ephrin-A2 may lead to abnormal connectivity in regions known for their involvement in reversal learning and perseverative behaviours, including thalamic–prefrontal cortical–striatal circuitry and particularly orbitofrontal cortex. The implication is that topographic organisation of higher order brain regions may play an important role in learning and decision making.