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.