Adaptation to a novel visuomotor transformation has revealed important principles regarding learning and memory. Computational and behavioral studies have suggested that acquisition and retention of a new visuomotor transformation are distinct processes. However, this dissociation has never been clearly shown. Here, participants made fast reaching movements while unexpectedly a 30-degree visuomotor transformation was introduced. During visuomotor adaptation, subjects received cerebellar, primary motor cortex (M1) or sham anodal transcranial direct current stimulation (tDCS), a noninvasive form of brain stimulation known to increase excitability. We found that cerebellar tDCS caused faster adaptation to the visuomotor transformation, as shown by a rapid reduction of movement errors. These findings were not present with similar modulation of visual cortex excitability. In contrast, tDCS over M1 did not affect adaptation, but resulted in a marked increase in retention of the newly learnt visuomotor transformation. These results show a clear dissociation in the processes of acquisition and retention during adaptive motor learning and demonstrate that the cerebellum and primary motor cortex have distinct functional roles. Furthermore, they show that is possible to enhance cerebellar function using tDCS.
Although the role of PGE2 in maintaining ductus arteriosus (DA) patency is well established, the specific PGE2 receptor subtype(s) (EP) involved have not been clearly identified. We used late gestation fetal and neonatal lambs to study developmental regulation of EP receptors. In the fetal DA, radioligand binding and RT-PCR assays virtually failed to detect EP1 but detected EP2, EP3D, and EP4 receptors in equivalent proportions. In the newborn lamb, DA total density was one-third of that found in the fetus and only EP2 was detected. Stimulation of EP2 and EP4 increased cAMP formation and was associated with DA relaxation. Though stimulation of EP3 inhibited cAMP formation, it surprisingly relaxed the fetal DA both in vitro and in vivo. This EP3-induced relaxation was specifically diminished by the ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide. In conclusion, PGE2 dilates the late gestation fetal DA through pathways that involve either cAMP (EP2 and EP4) or K(ATP) channels (EP3). The loss of EP3 and EP4 receptors in the newborn DA is consistent with its decreased responsiveness to PGE2.
Motor learning during reaching not only recalibrates movement but can also lead to small but consistent changes in the sense of arm position. Studies have suggested that this sensory effect may be the result of recalibration of a forward model that associates motor commands with their sensory consequences. Here we investigated whether similar perceptual changes occur in the lower limbs after learning a new walking pattern on a split-belt treadmill--a task that critically involves proprioception. Specifically, we studied how this motor learning task affects perception of leg speed during walking, perception of leg position during standing or walking, and perception of contact force during stepping. Our results show that split-belt adaptation leads to robust motor aftereffects and alters the perception of leg speed during walking. This is specific to the direction of walking that was trained during adaptation (i.e., backward or forward). The change in leg speed perception accounts for roughly half of the observed motor aftereffect. In contrast, split-belt adaptation does not alter the perception of leg position during standing or walking and does not change the perception of stepping force. Our results demonstrate that there is a recalibration of a sensory percept specific to the domain of the perturbation that was applied during walking (i.e., speed but not position or force). Furthermore, the motor and sensory consequences of locomotor adaptation may be linked, suggesting overlapping mechanisms driving changes in the motor and sensory domains.
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