A computational study of synaptic mechanisms of partial memory transfer in cerebellar vestibulo-ocular-reflex learning

There is a debate regarding whether motor memory is stored in the cerebellar cortex, or the cerebellar nuclei, or both. Memory may be acquired in the cortex and then be transferred to the cerebellar nuclei. Based on a dynamical system modeling with a minimal set of variables, we theoretically investigated possible mechanisms of memory transfer and consolidation in the context of vestibulo-ocular reflex learning. We tested different plasticity rules for synapses in the cerebellar nuclei and took robustness of behavior against parameter variation as the criterion of plausibility of a model variant. In the most plausible scenarios, mossy-fiber nucleus-neuron synapses or Purkinje-cell nucleus-neuron synapses are plastic on a slow time scale and store permanent memory, whose content is passed from the cerebellar cortex storing transient memory. In these scenarios, synaptic strengths are potentiated when the mossy-fiber afferents to the nuclei are active during a pause in Purkinje-cell activities. Furthermore, assuming that mossy fibers create a limited variety of signals compared to parallel fibers, our model shows partial memory transfer from the cortex to the nuclei.     

The negative cell cycle regulator, Tob (transducer of ErbB-2), is involved in motor skill learning

Tob (transducer of ErbB-2) is a negative cell cycle regulator with anti-proliferative activity in peripheral tissues. Our previous study identified Tob as a protein involved in hippocampus-dependent memory consolidation (M.L. Jin, X.M. Wang, Y.Y. Tu, X.H. Zhang, X. Gao, N. Guo, Z.Q. Xie, G.P. Zhao, N.H. Jing, B.M. Li, Y.Yu, The negative cell cycle regulator, Tob (Transducer of ErbB-2), is a multifunctional protein involved in hippocampus-dependent learning and memory, Neuroscience 131 (2005) 647-659). Here, we provide evidence that Tob in the central nervous system is engaged in acquisition of motor skill. Tob has a relatively high expression in the cerebellum. Tob expression is up-regulated in the cerebellum after rats receive training on a rotarod-running task. Rats infused with Tob antisense oligonucleotides into the 4th ventricle exhibit a severe deficit in running on a rotating rod or walking across a horizontally elevated beam.     

Gait variability magnitude but not structure is altered in essential tremor

Essential tremor (ET) is a common tremor disorder affecting postural/action tremor of the upper extremities and midline. Recent research revealed a cerebellar-like deficit during tandem gait in persons with ET, though spatiotemporal variability during normal gait in ET has been relatively ignored. The first purpose of this study was to investigate gait variability magnitude and structure in ET as compared to healthy older adults (HOA). To address this issue, 11 ET and 11 age-matched HOAs walked on a treadmill for 5 min at preferred walking speeds. HOAs walked for an additional minute while speed-matched to an ET participant. The second purpose was to describe the clinical correlates of gait variability in this population. To address this aim, 31 persons with ET walked on a treadmill for 5 min and completed the Fahn–Tolosa–Marin Tremor Rating Scale. Gait variability magnitude was derived by calculating coefficients of variation in stride length, stride time, step length, step time, and step width. Gait variability structure was derived using a detrended fluctuation analysis technique. At preferred walking speeds, ET participants walked significantly slower with significantly increased variability magnitude in all five spatiotemporal gait parameters. At speed-matched walking, ET participants exhibited significantly higher step width variability. Gait variability structure was not different between groups. We also observed that gait variability magnitude was predicted by severity of upper extremity and midline tremors. This study revealed that self-selected gait in ET is characterized by high variability that is associated with tremor severity in the upper extremity and midline.     

The control of wing kinematics by two steering muscles of the blowfly (Calliphora vicina)

We used a combination of high speed video and electrophysiological recordings to investigate the relationship between wing kinematics and the firing patterns of the first (b1) and second (b2) basalar muscles of tethered flying blowflies (Calliphora vicina). The b1 typically fires once during every wing stroke near the time of the dorsal stroke reversal. The b2 fires either intermittently or in bursts that may be elicited by a visual turning stimulus. Sustained activation of the b1 at rates near wing beat frequency appears necessary for the tonic maintenance of stroke amplitude. In addition, advances in the phase of b1 activation were correlated with both increased wing protraction during the down-stroke and increased stroke amplitude. Similar kinematic alterations were correlated with b2 spikes, and consequently, both muscles may function in the control of turns toward the contralateral side. The effects of the two muscles were evident within a single stroke period and decayed quickly. Kinematic changes correlated with b1 phase shifts were graded, suggesting a role in compensatory course stabilization. In contrast, b2 spikes were correlated with all-or-none changes in the wing stroke, a characteristic consistent with a role in mediating rapid turns towards or away from objects.Abbreviations b1 first basalar muscle - b2 second basalar muscle - PWP pleural wing process - RS radial stop - S wing span · - angle between the stroke plane and the longitudinal body axis - stroke amplitude - stroke elevation - L wing length - b1 phase of b1 activation - b2 phase of b2 activation - stroke deviation     

Abdominal muscle activation changes if the purpose is to control pelvis motion or thorax motion

The aim of this study was to compare trunk muscular recruitment and lumbar spine kinematics when motion was constrained to either the thorax or the pelvis. Nine healthy women performed four upright standing planar movements (rotations, anterior–posterior translations, medial–lateral translations, and horizontal circles) while constraining pelvis motion and moving the thorax or moving the pelvis while minimizing thorax motion, and four isometric trunk exercises (conventional curl-up, reverse curl-up, cross curl-up, and reverse cross curl-up). Surface EMG (upper and lower rectus abdominis, lateral and medial aspects of external oblique, internal oblique, and latissimus dorsi) and 3D lumbar displacements were recorded. Pelvis movements produced higher EMG amplitudes of the oblique abdominals than thorax motions in most trials, and larger lumbar displacements in the medial–lateral translations and horizontal circles. Conversely, thorax movements produced larger rotational lumbar displacement than pelvis motions during rotations and higher EMG amplitudes for latissimus dorsi during rotations and anterior–posterior translations and for lower rectus abdominis during the crossed curl-ups. Thus, different neuromuscular compartments appear when the objective changes from pelvis to thorax motion. This would suggest that both movement patterns should be considered when planning spine stabilization programs, to optimize exercises for the movement and muscle activations desired.     

Influence of haptic guidance in learning a novel visuomotor task

In (re)learning of movements, haptic guidance can be used to direct the needed adaptations in motor control. Haptic guidance influences the main driving factors of motor adaptation, execution error, and control effort in different ways. Human-control effort is dissipated in the interactions that occur during haptic guidance. Minimizing the control effort would reduce the interaction forces and result in adaptation. However, guidance also decreases the magnitude of the execution errors, which could inhibit motor adaptation. The aim of this study was to assess how different types of haptic guidance affect kinematic adaptation in a novel visuomotor task. Five groups of subjects adapted to a reaching task in which the visual representation of the hand was rotated 30°. Each group was guided by a different force field. The force fields differed in magnitude and direction in order to discern the adaptation based on execution errors and control effort. The results demonstrated that the execution error did indeed play a key role in adaptation. The more the guiding forces restricted the occurrence of execution errors, the smaller the amount and rate of adaptation. However, the force field that enlarged the execution errors did not result in an increased rate of adaptation. The presence of a small amount of adaptation in the groups who did not experience execution errors during training suggested that adaptation could be driven on a much slower rate and on the basis of minimization of control effort as was evidenced by a gradual decrease of the interaction forces during training. Remarkably, also in the group in which the subjects were passive and completely guided, a small but significant adaptation occurred. The conclusion is that both minimization of execution errors and control effort drives kinematic adaptation in a novel visuomotor task, but the latter at a much slower rate.     

A model of force and impedance in human arm movements

This paper describes a simple computational model of joint torque and impedance in human arm movements that can be used to simulate three-dimensional movements of the (redundant) arm or leg and to design the control of robots and human-machine interfaces. This model, based on recent physiological findings, assumes that (1) the central nervous system learns the force and impedance to perform a task successfully in a given stable or unstable dynamic environment and (2) stiffness is linearly related to the magnitude of the joint torque and increased to compensate for environment instability. Comparison with existing data shows that this simple model is able to predict impedance geometry well.     

Analysis and Neural Network Modeling of the Nonlinear Correlates of Habituation in the Vestibulo-ocular Reflex

Through the process of habituation, continued exposure to low-frequency (0.01 Hz) rotation in the dark produced suppression of the low-frequency response of the vestibulo-ocular reflex (VOR) in goldfish. The response did not decay gradually, as might be expected from an error-driven learning process, but displayed several nonlinear and nonstationary features. They included asymmetrical response suppression, magnitude-dependent suppression for lower- but not higher-magnitude head rotations, and abrupt-onset suppressions suggestive of a switching mechanism. Microinjection of lidocaine into the vestibulocerebellum of habituated goldfish resulted in a temporary dishabituation. This suggests that the vestibulocerebellum mediates habituation, presumably through Purkinje cell inhibition of vestibular nuclei neurons. The habituated VOR data were simulated with a feed-forward, nonlinear neural network model of the VOR in which only Purkinje cell inhibition of vestibular nuclei neurons was varied. The model suggests that Purkinje cell inhibition may switch in to introduce nonstationarities, and cause asymmetry and magnitude-dependency in the VOR to emerge from the essential nonlinearity of vestibular nuclei neurons.     

Sparse cerebellar innervation can morph the dynamics of a model oculomotor neural integrator

The oculomotor integrator is a brainstem neural network that converts velocity signals into the position commands necessary for eye-movement control. The cerebellum can independently adjust the amplitude of eye-movement commands and the temporal characteristics of neural integration, but the percentage of integrator neurons that receive cerebellar input is very small. Adaptive dynamic systems models, configured using the genetic algorithm, show how sparse cerebellar inputs could morph the dynamics of the oculomotor integrator and independently adjust its overall response amplitude and time course. Dynamic morphing involves an interplay of opposites, in which some model Purkinje cells exert positive feedback on the network, while others exert negative feedback. Positive feedback can be increased to prolong the integrator time course at virtually any level of negative feedback. The more these two influences oppose each other, the larger become the response amplitudes of the individual units and of the overall integrator network. Action Editor: Jonathan D. Victor     

正弦偏心旋转诱发的豚鼠前庭眼动反射特点

目的:观察豚鼠于不同频率和偏心半径正弦旋转时相对于轴心旋转的前庭眼动反射变化特点,以提取反映前庭耳石器功能的指标,为建立其功能检测方法提供依据。方法:采用频率0.1,0.2,0.3,0.4,0.5,0.6Hz,峰速60°/s的正弦旋转刺激,分别将豚鼠置于轴心,头向外偏心半径330mm,660mm,990mm处诱发其眼震,分析不同刺激条件下的眼震增益变化规律。结果:频率和偏心半径都对眼震的增益有显著影响:同一偏心半径条件下,眼震增益随频率增加而增大;同一频率条件下,眼震增益随偏心半径增加而增大,以在0.3Hz,0.4Hz最为明显,超过此频率范围后增益随半径变化不明显。结论:提取眼震增益的增强率(enhancementratio,ER)可以表达眼震增益随偏心半径增加而增大的增强效应,并作为反映豚鼠前庭耳石器功能的指标,以0.4Hz,半径990mm的正弦旋转模式作为耳石器功能评价的刺激模式较好。     

Detection of Cystathionine Ketimine in Bovine Cerebellum

A new sulfur-containing cyclic imino acid, cystathionine ketimine, has been detected in bovine cerebellum by gas chromatography, gas chromatography-mass spectrometry, and high pressure liquid chromatography procedures. Gas chromatography and gas-mass analyses are based on derivatization of endogenous cystathionine ketimine with diazomethane after a simple enrichment procedure. The high pressure liquid chromatography procedure takes advantage of the selective absorbance at 380 nm of the phenyl isothiocyanate-ketimine interaction product. The concentration of this new sulfur imino acid found in a pool of four bovine cerebella is approximately 0.5 nmol/g.     

Functional origins of the vertebrate cerebellum from a sensory processing antecedent

The structure of the cerebellar cortex is remarkably similar across vertebrate phylogeny. It is well developed in basaljawed fishes, such as sharks and rays with many of the same cell types and organizational features found in other vertebrategroups, including mammals. In particular, the lattice-like organization of cerebellar cortex (with a molecular layer of parallel fibres,interneurons, spiny Purkinje cell dendrites, and climbing fires) is a common defining characteristic. In addition to the cerebell...     

Severe impairment of cerebellum development in mice expressing a dominant-negative mutation inactivating thyroid hormone receptor alpha1 isoform

Thyroid hormone deficiency is known to deeply affect cerebellum post-natal development. We present here a detailed analysis of the phenotype of a recently generated mouse model, expressing a dominant-negative TRα1 mutation. Although hormonal level is not affected, the cerebellum of these mice displays profound alterations in neuronal and glial differentiation, which are reminiscent of congenital hypothyroidism, indicating a predominant function of this receptor isoform in normal cerebellum development. Some of the observed effects might result from the cell autonomous action of the mutation, while others are more likely to result from a reduction in neurotrophic factor production.     

Tenascins are associated with lipid rafts isolated from mouse brain

Lipid rafts are microdomains of the plasma membrane which are enriched in glycosphingolipids and specific proteins. The reported interactions of several raft-associated proteins (such as, e.g., F3) with tenascin C and tenascin R prompted us to consider that these oligomeric multidomain glycoproteins of the extracellular matrix (ECM) could associate with rafts. Here, we show punctate immunocytochemical distributions of tenascin C (TN-C) and tenascin R (TN-R) at the membrane surface of neural cells resembling the pattern reported for raft-associated proteins. Moreover, cholesterol depletion with methyl-beta-cyclodextrin reduced the punctate surface staining of TN-C. Consistently, TN-C was associated with lipid rafts of neonatal mouse brain according to sucrose density gradient centrifugation experiments. Furthermore, TN-R was also found in rafts prepared from myelin of adult mice. Thus, brain-derived tenascins are able to associate with lipid rafts.