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At least 289 records · Page 16Linked to original sources
PubMed2001

The cerebellum-specific Munc13 isoform Munc13-3 regulates cerebellar synaptic transmission and motor learning in mice.

Munc13 proteins form a family of three, primarily brain-specific phorbol ester receptors (Munc13-1/2/3) in mammals. Munc13-1 is a component of presynaptic active zones in which it acts as an essential synaptic vesicle priming protein. In contrast to Munc13-1, which is present in most neurons throughout the rat and mouse CNS, Munc13-3 is almost exclusively expressed in the cerebellum. Munc13-3 mRNA is present in granule and Purkinje cells but absent from glia cells. Munc13-3 protein is localized to the synaptic neuropil of the cerebellar molecular layer but is not found in Purkinje cell dendrites, suggesting that Munc13-3, like Munc13-1, is a presynaptic protein at parallel fiber-Purkinje cell synapses. To examine the role of Munc13-3 in cerebellar physiology, we generated Munc13-3-deficient mutant mice. Munc13-3 deletion mutants exhibit increased paired-pulse facilitation at parallel fiber-Purkinje cell synapses. In addition, mutant mice display normal spontaneous motor activity but have an impaired ability to learn complex motor tasks. Our data demonstrate that Munc13-3 regulates synaptic transmission at parallel fiber-Purkinje cell synapses. We propose that Munc13-3 acts at a similar step of the synaptic vesicle cycle as does Munc13-1, albeit with less efficiency. In view of the present data and the well established vesicle priming function of Munc13-1, it is likely that Munc13-3-loss leads to a reduction in release probability at parallel fiber-Purkinje cell synapses by interfering with vesicle priming. This, in turn, would lead to increases in paired-pulse facilitation and could contribute to the observed deficit in motor learning.

Animals↗
PubMed1999

Coherence of sequential movements and motor learning.

The analysis of oscillatory EEG phenomena such as interregional coherence (task-related coherence [TRCoh] or event-related coherence) has advanced our knowledge of neurophysiological processes underlying the performance and learning of skilled finger movements. It has become clear that various types of higher task demands are reflected by changes in the functional coupling of different cortical areas and not only by changes in regional activation. Neuroscientists are merely starting to understand how coherent oscillations might encode information in the human motor system ("sensorimotor binding") and how well this can be measured from the surface EEG. However, interregional coherence is a potentially independent mechanism that can, up to now, only be investigated with electrophysiological techniques such as EEG and MEG. The studies reviewed below focus on coherence of finger movements and motor learning: increasing complexity of a movement sequence, internal rhythm generation, visuomotor integration, deficits in interhemispheric coupling, and bimanual coordination. Evidence is presented for a special functional significance of TRCoh in the beta frequency range (13 to 21 Hz) for information processing in large-scale sensorimotor networks during motor tasks.

Electroencephalography↗
PubMed1978

Shifts in attention demands and motor program utilization during motor learning.

The relationship between changes in the level of motor program utilization and attention demand during the learning of a motor task was examined. The primary task involved an 86-cm horizontal arm movement which subjects attempted to complete coincident with the end of a 360 degrees sweep of a clock hand. A secondary task performed with the opposite limb required a rapid button press to an auditory probe stimulus presented at various temporal locations within each trial. Control subjects performed either the primary task or the secondary task alone, while experimental subjects performed both tasks in combination. Schmidt's (1972) index of preprogramming was used to measure the level of motor program utilization, while probe reaction time reflected the attention demand of the primary task. There was a stable level of motor programming over four consecutive days of practice (100 trials a day), but a general decrease in attention demand. Implications for an expansion of the concept of the motor program were discussed.

Journal Article↗
PubMedDate not supplied

Spectral analysis of electroencephalogram during perceptual-motor learning.

Spectral analysis of the electroencephalogram was utilized to determine attention demands during learning of a perceptual motor task. Fifteen subjects participated in the task which consisted of 15 trials of the mirror star learning task. EEG was monitored bilaterally from the occipital and parietal lobes during each trial and analyzed for intensity and mean frequency components within five different bandwidths. All subjects rapidly improved performance in terms of both time and error reduction although the former measure appeared to be a better fit of the supradiagonal form of matrix typically found for this type of learning. Mean alpha frequency increased slightly during the task while delta frequency decreased.

Adolescent↗
PubMed2006

Importance of K+-dependent Na+/Ca2+-exchanger 2, NCKX2, in motor learning and memory.

Plasma membrane Na+/Ca2+-exchangers play a predominant role in Ca2+ extrusion in brain. Neurons express several different Na+/Ca2+-exchangers belonging to both the K+-independent NCX family and the K+-dependent NCKX family. The unique contributions of each of these proteins to neuronal Ca2+ homeostasis and/or physiology remain largely unexplored. To address this question, we generated mice in which the gene encoding the abundant neuronal K+ -dependent Na+/Ca2+-exchanger protein, NCKX2, was knocked out. Analysis of these animals revealed a significant reduction in Ca2+ flux in cortical neurons, a profound loss of long term potentiation and an increase in long term depression at hippocampal Schaffer/CA1 synapses, and clear deficits in specific tests of motor learning and spatial working memory. Surprisingly, there was no obvious loss of photoreceptor function in cones, where expression of the NCKX2 protein had been reported previously. These data emphasize the critical and non-redundant role of NCKX2 in the local control of neuronal [Ca2+] that is essential for the development of synaptic plasticity associated with learning and memory.

Animals↗
PubMed2002

Cluster analysis of activity-time series in motor learning.

Neuroimaging studies of learning focus on brain areas where the activity changes as a function of time. To circumvent the difficult problem of model selection, we used a data-driven analytic tool, cluster analysis, which extracts representative temporal and spatial patterns from the voxel-time series. The optimal number of clusters was chosen using a cross-validated likelihood method, which highlights the clustering pattern that generalizes best over the subjects. Data were acquired with PET at different time points during practice of a visuomotor task. The results from cluster analysis show practice-related activity in a fronto-parieto-cerebellar network, in agreement with previous studies of motor learning. These voxels were separated from a group of voxels showing an unspecific time-effect and another group of voxels, whose activation was an artifact from smoothing.

Adult↗
PubMed2001

Frames of reference in perceptual-motor learning: evidence from a blind manual positioning task.

Participants moved a joystick to bring a computer-displayed cursor to each of six on-screen target locations arrayed around the center of the screen. At the start of each trial, the stick rested vertically, with a cursor occupying the center of the screen. A target appeared at another location and as soon as the stick was moved away from its rest position the cursor disappeared until the participant pressed a trigger on the stick to indicate when s/he thought the stick-controlled cursor was at the target site. With training, participants improved on the blind positioning task, but when conditions changed their performance suffered. Changing the hand used in the task or the location of the stick caused approximately equal disruptions, but changing both hand and location was significantly more disruptive than changing just one feature. The results support the hypothesis that perceptual-motor learning entails coding of extrinsic (spatial coordinates) as well as intrinsic (postural or body movement) information.

Analysis of Variance↗
PubMed2005

The representation of time for motor learning.

We have identified factors that control precise motor timing by studying learning in smooth pursuit eye movements. Monkeys tracked a target that moved horizontally for a fixed time interval before changing direction through the addition of a vertical component of motion. After repeated presentations of the same target trajectory, infrequent probe trials of purely horizontal target motion evoked a vertical eye movement around the time when the change in target direction would have occurred. The pursuit system timed the vertical eye movement by keeping track of the duration of horizontal target motion and by measuring the distance the target traveled before changing direction, but not by learning the position in space where the target changed direction. We conclude that high temporal precision in motor output relies on multiple signals whose contributions to timing vary according to task requirements.

Animals↗
PubMed1997

Neuroserpin, a brain-associated inhibitor of tissue plasminogen activator is localized primarily in neurons. Implications for the regulation of motor learning and neuronal survival.

A cDNA clone for the serine proteinase inhibitor (serpin), neuroserpin, was isolated from a human whole brain cDNA library, and recombinant protein was expressed in insect cells. The purified protein is an efficient inhibitor of tissue type plasminogen activator (tPA), having an apparent second-order rate constant of 6. 2 x 10(5) M-1 s-1 for the two-chain form. However, unlike other known plasminogen activator inhibitors, neuroserpin is a more effective inactivator of tPA than of urokinase-type plasminogen activator. Neuroserpin also effectively inhibited trypsin and nerve growth factor-gamma but reacted only slowly with plasmin and thrombin. Northern blot analysis showed a 1.8 kilobase messenger RNA expressed predominantly in adult human brain and spinal cord, and immunohistochemical studies of normal mouse tissue detected strong staining primarily in neuronal cells with occasionally positive microglial cells. Staining was most prominent in the ependymal cells of the choroid plexus, Purkinje cells of the cerebellum, select neurons of the hypothalamus and hippocampus, and in the myelinated axons of the commissura. Expression of tPA within these regions is reported to be high and has previously been correlated with both motor learning and neuronal survival. Taken together, these data suggest that neuroserpin is likely to be a critical regulator of tPA activity in the central nervous system, and as such may play an important role in neuronal plasticity and/or maintenance.

Animals↗
PubMed2005

The impact of mild closed head injury on involuntary saccadic adaptation: evidence for the preservation of implicit motor learning.

OBJECTIVE: Mild closed head injury (CHI) can impair performance on volitional saccades (fast eye movements), with poorer saccade accuracy being one of the principal deficits. Assessing a patient group with known deficits of volitional saccades, the authors investigated whether mild CHI similarly impairs the implicit adaptation of visually-guided (reflexive) saccades, an important process which maintains saccadic accuracy. METHODS: Within 2 weeks following mild CHI, 30 patients and 30 matched controls were compared on a computerized paradigm, which artificially induced saccadic adaptation. In response to an initial stimulus, subjects made a saccade during which the stimulus was displaced centripetally causing the initial (primary) saccade to be inaccurate. While these intra-saccadic changes remained unnoticed by the subjects, the displacements gradually caused adaptive saccadic hypometria. RESULTS: No differences in adaptation were found between the CHI group and the controls (F(1, 29) = 0.51, p = 0.48). This finding indicates that mild CHI does not impair implicit reflexive saccade adaptation and suggests that cerebellar function and functions of deeper brain structures such as the thalamus, superior colliculus and the basal ganglia may be largely preserved following mild CHI. The current results support the notion that the profile of oculomotor function after mild CHI reflects a centripetal gradient of impairment and relates closely to the functional integrity of the injured brain.

Adaptation, Physiological↗
PubMed2006

Implications of assist-as-needed robotic step training after a complete spinal cord injury on intrinsic strategies of motor learning.

Robotic training paradigms that enforce a fixed kinematic control might be suboptimal for rehabilitative training because they abolish variability, an intrinsic property of neuromuscular control (Jezernik et al., 2003). In the present study we introduce "assist-as-needed" (AAN) robotic training paradigms for rehabilitation of spinal cord injury subjects. To test the efficacy of these robotic control strategies to teach spinal mice to step, we divided 27 adult female Swiss-Webster mice randomly into three groups. Each group was trained robotically by using one of three control strategies: a fixed training trajectory (Fixed group), an AAN training paradigm without interlimb coordination (Band group), and an AAN training paradigm with bilateral hindlimb coordination (Window group). Beginning at 14 d after a complete midthoracic spinal cord transection, the mice were trained daily (10 min/d, 5 d/week) to step on a treadmill 10 min after the administration of quipazine (0.5 mg/kg), a serotonin agonist, for a period of 6 weeks. During weekly performance evaluations, the mice trained with the AAN window paradigm generally showed the highest level of recovery as measured by the number, consistency, and periodicity of steps during the testing sessions. In all three measurements there were no significant differences between the Band and the Fixed training groups. These results indicate that the window training approach, which includes loose alternating interlimb coordination, is more effective than a fixed trajectory paradigm with rigid alternating interlimb coordination or an AAN paradigm without any interlimb constraints in promoting robust postinjury stepping behavior.

Animals↗