A clue to what this alternative learning mechanism might be was provided by a recent study in which healthy subjects were exposed to an incremental rotation but were provided only with binary reward rather than vector error (Izawa and Shadmehr, 2011). Under these circumstances, subjects showed exploratory trial-and-error behavior rather Everolimus mouse than typical monotonic adaptation behavior and also did not show a change in perceived hand

position. These two sets of results in humans are consistent with the idea that errors can be reduced through cerebellar-independent non-forward model-based processes as long as the errors lie within the envelope of exploratory variability. A study of saccadic gain adaptation in monkeys also showed a small amount of residual adaptation to a gain change after lesions of the oculomotor posterior vermis (Barash et al., 1999). The authors of this study could only speculate as to the locus for this residual capacity to reduce errors, suggesting it might be mediated by the cerebellar nuclei. We would suggest that this result in monkeys is reminiscent of Bosutinib clinical trial the human reaching studies reported above and that the mechanism might

be outside the cerebellum. Support for this idea comes from studies in monkeys, in which intermediate and lateral deep cerebellar nuclei ablations were performed and yet slow recovery of limb ataxia was still seen, which was reversed with lesions to sensory cortex (Mackel, 1987). Compared to the cerebellum, the precise role of the basal ganglia in motor learning remains unclear and contradictory. Like

the cerebellum, both the anatomy and neurotransmitter localization for the basal ganglia (BG) are highly conserved in all vertebrates, again suggesting a preserved form of computation (Reiner et al., 1998). Of particular interest, is the fact that basal ganglia output evolved from principally Oxalosuccinic acid targeting the tectum in amphibians to also targeting cortical regions in reptiles and in subsequent vertebrates (Reiner et al., 1998). In addition, there is no evidence for either cortical or significant dopaminergic inputs to striatum in amphibians. Amphibians have simpler musculoskeletal systems and execute a simpler repertoire of movements than reptiles; their movements are tectally mediated, stereotypical, and stimulus locked (Reiner et al., 1998). This phylogenetic transition between amphibians and reptiles with respect to the connections of the BG is interesting for a number of reasons. First, it suggests that the BG perform a function that does not have an obligate relationship to cortex.