Jeremy Wong

Somatosensory Plasticity and Motor Learning

Motor learning is dependent upon plasticity in motor areas of the brain, but does it occur in isolation, or does it also result in changes to sensory systems? We examined changes to somatosensory function that occur in conjunction with motor learning. We found that even after periods of training as brief as 10 min, sensed limb position was altered and the perceptual change persisted for 24 h. The perceptual change was reflected in subsequent movements; limb movements following learning deviated from the prelearning trajectory by an amount that was not different in magnitude and in the same direction as the perceptual shift. Crucially, the perceptual change was dependent upon motor learning. When the limb was displaced passively such that subjects experienced similar kinematics but without learning, no sensory change was observed. The findings indicate that motor learning affects not only motor areas of the brain but changes sensory function as well.

Estrogen receptor ? immunoreactivity in differentiating cells of the developing rat cerebellum

Estrogen receptors (ER) play a significant role in the development of some regions of the mammalian brain. Recently, ER‐beta (ERβ) mRNA and protein were shown to be expressed in the rat cerebellum. In the present study, the ontogeny of ERβ protein expression was examined in the rat cerebellum during postnatal development. Western blot analysis indicated that a single ERβ‐like immunoreactive species of ∼55 kDa was present in protein lysates prepared from the cerebella of female and male Sprague‐Dawley rat pups. Immunocytochemical analysis of cerebellar sections from the midline vermis revealed that during development, the expression of ERβ varied with age and cell‐type, but not sex. In the developing cerebellum, highest levels of ERβ‐immunoreactivity (IR) were detected in neurons during neurite growth, and in some glia during migration. Throughout the first postnatal week, ERβ‐IR was localized to differentiating granule cells in the external germinal layer and to migrating glia. Differentiating granule cells expressed detectable levels of ERβ throughout development. In Purkinje cells, ERβ‐IR was first detected on postnatal day 6 (P6), with peak intensities of immunostaining coinciding with the initiation of axonal and dendritic growth that occurs between P7 and P8. Expression of ERβ‐IR remained high during maturation of Purkinje cell dendrites, and then decreased to a lower level maintained in the adult. From the third postnatal week, ERβ‐IR was also detected in the later developing Golgi, stellate, and basket neurons. These results suggest that ERβ may play a role in growth‐related mechanisms during differentiation of cerebellar neurons and glia. J. Comp. Neurol. 430:396–409, 2001.

Visual Cues Signaling Object Grasp Reduce Interference in Motor Learning

Recent motor learning studies show that human subjects and nonhuman primates form neural representations of novel mechanical environments and associated forces. Whereas proficient adaptation is seen for a single force field, when faced with multiple novel force environments, movement performance and in particular the ability to switch between different force environments declines. It is difficult to reconcile these findings with the notion that primates can proficiently switch between multiple motor skills. Conceivably, particular kinds of sensory, cognitive, or perceptual contextual cues are required. This study examined the effect of visual feedback on motor learning, in particular, cues that simulated interaction with a virtual object. A robot arm was used to deliver novel patterns of forces (force fields) to the limb during reaching movements. We tested the possibility that subjects transition more easily between novel forces and their sudden absence when they are accompanied by visual cues that relate to object grasp. We used a virtual display system to present subjects with different kinds of visual feedback during reaching, including illusory feedback, indicating grasp of a virtual object during reaching in the force field, and object release in the absence of forces. Throughout the experiment, subjects in fact maintained grasp of the robot. We found that, indeed, the most effective visual cues were those associating the force field with grasp of the virtual object and the absence of the force field with release of the object. Our findings show more broadly that specific visual cues can protect motor skills from interference.

Simplified serum- and steroid-free culture conditions for high-throughput viability analysis of primary cultures of cerebellar granule neurons.

A serum- and steroid-free primary culture system was developed for the maintenance and automated analysis of cerebellar granule cell viability. Conventional poly-lysine coated 96-well tissue culture plates serve as a platform for growth, experimental manipulation and subsequent automated analysis of these primary cultured neurons. Cerebellar granule neurons were seeded at densities ranging from 2 x 10(4) to 1.25 x 10(6) cells/cm(2) and maintained in serum- and steroid-free culture conditions for 7 days. Viability was subsequently determined by the reduction of [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), and the degree of cell death occurring over that period was determined by the release of lactate dehydrogenase (LDH). At appropriate cell densities, the results of the MTS reduction and LDH release assays were directly proportional to the initial number of cerebellar granule cells plated. Those results indicate that an initial cell density of 0.5 - 1.0 x 10(5) cells per well (0.32 cm(2)) was appropriate for simultaneous analysis with the MTS reduction and LDH release assays. Both assays were then used to demonstrate the utility of this model system for analysis of tert-butyl-hydroperoxide and hydrogen peroxide induced oxidative stress. Additionally, the MTS reduction assay was used to demonstrate that the NMDA-receptor selective antagonist MK-801 was neuroprotective against glutamate-mediated excitotoxicity. This study defines a powerful and flexible primary culture system for cerebellar neurons that is useful for high-throughput analysis of factors that influence neuronal viability.

Limb stiffness is modulated with spatial accuracy requirements during movement in the absence of destabilizing forces.

The motor system can use a number of mechanisms to increase movement accuracy and compensate for perturbing external forces, interaction torques, and neuromuscular noise. Empirical studies have shown that stiffness modulation is one adaptive mechanism used to control arm movements in the presence of destabilizing external force loads. Other work has shown that arm muscle activity is increased at movement end for reaching movements to small visual targets and that changes in stiffness at movement end are oriented to match changes in visual accuracy requirements such as target shape. In this study, we assess whether limb stiffness is modulated to match spatial accuracy requirements during movement, conveyed using visual stimuli, in the absence of external force loads. Limb stiffness was estimated in the middle of reaching movements to visual targets located at the end of a narrow (8 mm) or wide (8 cm) visual track. When greater movement accuracy was required, we observed modest but reliable increases in limb stiffness in a direction perpendicular to the track. These findings support the notion that the motor system uses stiffness control to augment movement accuracy during movement and does so in the absence of external unstable force loads, in response to changing accuracy requirements conveyed using visual cues.

The Influence of Visual Perturbations on the Neural Control of Limb Stiffness

To adapt to novel unstable environments, the motor system modulates limb stiffness to produce selective increases in arm stability. The motor system receives information about the environment via somatosensory and proprioceptive signals related to the perturbing forces and visual signals indicating deviations from an expected hand trajectory. Here we investigated whether subjects modulate limb stiffness during adaptation to a purely visual perturbation. In a first experiment, measurements of limb stiffness were taken during adaptation to an elastic force field (EF). Observed changes in stiffness were consistent with previous reports: subjects increased limb stiffness and did so only in the direction of the environmental instability. In a second experiment, stiffness changes were measured during adaptation to a visual perturbing environment that magnified hand-path deviations in the lateral direction. In contrast to the first experiment, subjects trained in this visual task showed no accompanying change in stiffness, despite reliable improvements in movement accuracy. These findings suggest that this sort of visual information alone may not be sufficient to engage neural systems for stiffness control, which may depend on sensory signals more directly related to perturbing forces, such as those arising from proprioception and somatosensation.