, 2010). Further evidence for the claim that learning of motor skill results from changes in representation in motor cortex comes from experiments in rats. In a specially designed reach to grasp task, performance improvements are accompanied by various structural changes in M1 (Whishaw and Pellis, 1990). It has also been shown that the signal-to-noise ratio in spiking

M1 neurons improves with practice on a reach-to-grasp task (Kargo and Nitz, 2004). Recently it has been shown that destroying dopaminergic projections to motor cortex completely abolishes skill acquisition (Hosp et al., 2011), which suggests that a specific kind of learning (skill) needs Vismodegib to take place in M1 directly. Large lesions to motor cortex lead to permanent qualitative changes in skilled reaching, with recovery mediated through compensation (Metz et al., 2005 and Whishaw et al., 2008). In contrast, small strokes in motor cortex lead to significant recovery of premorbid prehension kinematics (Gonzalez and Kolb, 2003). This recovery seems to be mediated by plasticity in peri-infarct cortex, with structural

changes very similar to those described after reach training in healthy rats. Similar findings have been made in the squirrel monkey (Nudo et al., 1996). Thus M1 is necessary for recovery of previously acquired High Content Screening skills after small cortical lesions and acquisition of new skills, likely using very similar plasticity mechanisms. All these results taken together suggest that if skill is considered the ability to execute better movements of a given type rather than selecting

the right sequence of movements without emphasis on their quality, then the motor cortex is necessary if not sufficient. It is notable that simply repeating a movement stereotypically that does not Olopatadine require a skill change does not lead to map changes in motor cortex (Plautz et al., 2000). Finally, it should be emphasized that our contention that M1 is the necessary structure for learning skilled execution does not preclude M1 also being the location for the representation of stereotypies that are learned initially through BG-dependent processes. This “transfer” idea is favored by some investigators and supported by the decreasing LMAN dependence of learned songs in the songbird (Ölveczky et al., 2011). Here, we have briefly described experiments across humans and model systems in order to seek unifying functional principles with respect to the roles of the cerebellum, basal ganglia, and primary motor cortex in motor learning. Recently, a similar but more general computational synthesis of these areas has been proposed (Doya, 1999).