Effects of repeated ankle plantar-flexions on H-reflex and body sway during standing.

The study investigated relations between effects of repeated ankle plantar-flexion movements exercise on the soleus Hoffmann (H) reflex and on postural body sway when maintaining upright stance. Ten young volunteers performed five sets of ankle plantar-flexions of both lower limbs. Assessment of the feet centre-of-pressure (COP) displacement and H-reflex tests were carried out in quiet stance before, during and after the exercise. H-max and M-max responses were obtained in 8 subjects and reported as the peak-to-peak amplitudes of the right soleus muscle electromyographic waves. Mean dispersion of COP along the antero-posterior direction increased significantly during the exercise; whilst the overall H-reflex response indicated a reduction without a concomitant modification in the M-max response. H-reflex responses, however, varied between participants during the first sets of exercise, showing two main trends of modulation: either depression or early facilitation followed by reduction of the H-reflex amplitude. The extent of reflex modulation in standing position was correlated to the concentric work performed during the exercise (r=0.85; p<0.01), but not to the antero-posterior COP dispersion. These results suggest that during a repeated ankle plantar-flexions exercise, modulation of the H-reflex measured in upright stance differs across individuals and is not related to changes of postural sway.

Comparison of neuronal activities of external cuneate nucleus, spinocerebellar cortex and interpositus nucleus during passive movements of the rat's forelimb.

In this paper we examined the neuronal activities of external cuneate nucleus, spinocerebellar Purkinje cells and interpositus nucleus during passive forelimb movements in anesthetized rats with the aim of identifying common or different patterns of activation across structures. By means of principal components analysis, we identified two main patterns of discharge which explained most of the dataset variance. One component characterized the movement-related activity of external cuneate and spinocerebellar cortical neurons, while the other reflected neuronal activity of the interpositus nucleus. We also found that both principal components were related to global forelimb kinematics but, while most of the variance of the activity of external cuneate cells and spinocerebellar Purkinje cells was explained by the limb axis orientation and orientation velocity, interpositus neurons' firing was best related to length and length velocity. This difference in the forelimb kinematics representation observed in external cuneate nucleus and spinocerebellar cortex compared with the interpositus nucleus is discussed with respect to the specific role that these structures may play also during active control of limb movements.

Spatial anisotropy in the encoding of three-dimensional passive limb position by the spinocerebellum.

In an earlier study, we found that the encoding of limb position in the sagittal plane across the population of spinocerebellar Purkinje cells was anisotropic with a preferential gradient along horizontal direction. The aim of this study was to extend to a three-dimensional (3D) workspace the analysis of the relationships between Purkinje cells activity and rat's forelimb spatial position. In anesthetized animals, the extracellular activity of 121 neurons was recorded while a robot passively placed the limb in 18 positions within a cubic workspace (3x3x3 cm). In order to characterize the relationship between spatial locations and Purkinje cell activity we performed a backward stepwise regression starting from a model with three independent variables representing the antero-posterior, the medial-lateral and the vertical axes of workspace. Regression analysis showed that the firing of most cells was modulated exclusively along the antero-posterior (25%) or the medial-lateral (38%) axis, while a small portion was related only to the vertical axis (8%), indicating a generalized nonuniform sensitivity of Purkinje cells to limb displacement in 3D space.

Control of head stability during gait initiation in young and older women.

Transition tasks between static and dynamic situations may challenge head stabilization and balance in older individuals. The study was designed to investigate differences between young and older women in the upper body motion during the voluntary task of gait initiation. Seven young (25+/-2.3 years) and seven older healthy women (78+/-3.4 years) were required to stand on a force platform and initiate walking at their self-selected preferred speed. Angles of head, neck and trunk were measured by motion analysis in the sagittal plane and a cross-correlation analysis was performed on segments pairs. Variability of head and neck angular displacements, as indicated by average standard deviation, was significantly greater in the older than in the young participants. The young women maintained dynamic stability of the upper body, as forward flexion of the trunk was consistently counteracted by coordinated head-neck extension. Differently, movement patterns employed by the older women also included a rigid motion of all upper body segments leaning forward as a single unit. These results demonstrated that older women perform the transition from standing to walking with greater variability in the patterns of upper body motion compared to young women.

Neuromuscular junction disassembly and muscle fatigue in mice lacking neurotrophin-4.

Neurotrophin-4 (NT-4) is produced by slow muscle fibers in an activity-dependent manner and promotes growth and remodeling of adult motorneuron innervation. However, both muscle fibers and motor neurons express NT-4 receptors, suggesting bidirectional NT-4 signaling at the neuromuscular junction. Mice lacking NT-4 displayed enlarged and fragmented neuromuscular junctions with disassembled postsynaptic acetylcholine receptor (AChR) clusters, reduced AChR binding, and acetylcholinesterase activity. Electromyographic responses, posttetanic potentiation, and action potential amplitude were also significantly reduced in muscle fibers from NT-4 knock-out mice. Slow-twitch soleus muscles from these mice fatigued twice as rapidly as those from wild-type mice during repeated tetanic stimulation. Thus, muscle-derived NT-4 is required for maintenance of postsynaptic AChR regions, normal muscular electrophysiological responses, and resistance to muscle fatigue. This neurotrophin may therefore be a key component of an activity-dependent feedback mechanism regulating maintenance of neuromuscular connections and muscular performance.

Distribution of spinocerebellar Purkinje cell responses to passive forelimb movements in the rat.

We recorded Purkinje cell activity throughout the spinocerebellum of anaesthetized rats while imposing circular passive movements to the unrestrained forelimb. The aim was to understand the type of processing of sensory information occurring at the level of the cerebellar cortex, on the basis that precerebellar sensory neurons have been shown to represent whole limb movement parameters better than single joint movements. We observed that neurons representing sensory aspects of arm movements were scattered throughout the spinocerebellar cortex without a distinct segregation from those that did not respond, albeit the relative density of responsive and unresponsive neurons was quite variable and depended on the area of the cortex. Furthermore, Purkinje cells that responded significantly to the arm movement cycles all showed the same response pattern consisting of a firing rate increase during the downward extension of the arm. These results are discussed as suggesting a coordinate framework for the representation of proprioceptive information in the cerebellum congruent to that observed for encoding motor parameters.

C-Fos expression in the basilar pontine nuclei and reticulotegmental nucleus of the rat following lateral cerebellar nucleus stimulation.

The present study was carried out with the aim to observe whether, in the rat, the electric activation of the projection form the cerebellar lateral nucleus (LN) to the basilar pontine nuclei (BPN) and to the reticulotegmental nucleus (RtTg) is capable to induce the c-Fos expression. In particular, we compared the effects of a continuous LN stimulation at low-frequency (tonic stimulation) with those induced by high frequency pulse trains (phasic stimulation). The observed results show that the stimulation of LN induces c-Fos expression in a significant fraction of neurons in the contralateral BPN and RtTg. It was also observed that phasic stimulation was slightly more capable in producing c-Fos expression with respect to the tonic stimulation. Furthermore, systemic injection of MK-801, a non-competitive antagonist of the NMDA receptor, reduced the LN-induced c-Fos expression in BPN and RtTg. In contrast, GYKI 52466, an AMPA/kainate receptor antagonist, did not change the LN driven induction of c-Fos in both BPN and RtTg.

Involvement of the noradrenergic system in modulating the blink reflex in humans.

Several researches have shown that the spinal reflex transmission in animals, as well as humans, was inhibited by alpha(2)-agonists, due to a disfacilitation of tonic noradrenergic control on motoneuronal output. To understand better the mechanisms regulating certain aspects of motor activity, here we reinvestigated the possible role of noradrenergic systems in modulating reflex activity of the brainstem in humans. To this aim, blink reflex responses (R1 and R2) evoked by electrical stimulation of the supraorbital nerve were electromyographically recorded in healthy volunteers. Both R1 and R2 areas were measured at 10-min intervals before and after i.v. injection of alpha(2)-agonist clonidine (0.5 microg/kg). The substance induced consistent depression of R1, which reached its maximum 40 min after drug administration (-43% of the control values). Ipsilateral R2 area resulted little affected by clonidine (-15% at 50 min), whereas no effects were observed in contralateral R2. Blood pressure values were never altered by drug injections. These results, taken together with previous observations, support the hypothesis that alpha(2)-agonist substances may cause a transient inactivation of noradrenergic neurons, thus releasing neurons involved in the circuitry of the blink reflex from a facilitatory drive. Since clonidine differentially modulated blink reflex responses, it is likely to assume that such a disfacilitation concerns mostly pontine units mediating the R1. However, the complexity of clonidine's effects at multiple pre- and postsynaptic sites does not allow us to exclude that other systems are involved in the alpha(2)-mediated control of facial motoneurons.

Sensory representation of passive movement kinematics by rat's spinocerebellar Purkinje cells.

In this paper we examined Purkinje cells' sensory representations of kinematic parameters of passive movements imposed to the forelimb of anesthetized rats. Simple spike Purkinje cell activity was recorded while the rat's ipsilateral forearm was moved passively along circular footpaths at two different speeds. We found that the activity of 35.33% (165/467) of the neurons was significantly modulated during movement cycles. A multivariate regression analysis indicated that movement direction was the predominant factor in determining Purkinje cell activity, whereas movement velocity (i.e. the combination of movement direction and speed) was represented to a much lesser degree. Based on this result, we might suggest that a cortical efferent copy is necessary to the cerebellum in order to elaborate a movement velocity signal.

Cortical control of cerebellar dentato-rubral and dentato-olivary neurons.

The cortical input of 117 dentate nucleus neurons projecting either to the red nucleus (73 cells) or to the inferior olive (44 units) was studied electrophysiologically in rats. The majority of cells in both groups responded to electrical stimulation of discrete sites of the contralateral motor cortex. However, activation latencies from the same cortical focus were shorter for neurons projecting to the red nucleus than for olivary-projecting neurons. Principal components analysis pointed out significant differences between the two neuronal subgroups also in the temporal pattern of activity. These results suggest that a motor command might be transmitted through parallel independent channels to cerebellar neurons projecting to different regions of the brainstem.

On the relation of rat's external cuneate activity to global parameters of forelimb posture.

Using anesthetized adult rats, we studied the relationships between the activity of cells belonging to the external cuneate nucleus (ECN) and passive forelimb positions. In essence, we sought to distinguish between a representation of limb position based on local limb parameters (individual joint angles, for example) or a representation based on more global parameters such as the length and the orientation of the limb axis. Using multivariate regression analyses we found that most neurons showed strong linear relationships with the length and the orientation of the limb axis. Relationships to individual joint angles were, instead, rather weak and in most cases not significant. This result implies an extensive integration of sensory information at the level of second order sensory neurons.

Spinocerebellar Purkinje cells and rat forelimb postures: a direction-dependent activity.

On anesthetized adult rats, we examined the possibility that the discharges of spinocerebellar Purkinje cells (PCs) are modulated by passive limb positioning. The rat forelimb was passively placed in four different sagittal positions while the simple spike spontaneous activity of single PCs was recorded; recordings started 5 s after the reaching of the posture and the forelimb remained at each position for at least 30 s. Although the activity of the PCs did not reflect the forelimb position, it showed hysteresis that depended in a cosine fashion on the direction of the preceding movement. This implies that the directional sensitivity of spinocerebellar PCs is persistent, since the activity levels were almost constant throughout the recording time.

Influences exerted by the frontal eye field on accessory oculomotor nuclei neurons of the rat.

The medial agranular cortex (AGm), considered the rat's analogous to the frontal eye fields of the monkey, sends a conspicuous projection towards the accessory oculomotor nuclei (AON), i.e. the nucleus of posterior commissure (NPC), the nucleus of Darkschewitsch (NDK) and the interstitial nucleus of Cajal (INC). The nature of the synaptic influences exerted by AGm on the AON neurons and the receptor(s) which mediates these cortical-evoked effects were studied in adult rats. Electrical stimulation of a single site within the AGm elicited changes in firing rate of a significant fraction of cells belonging to the ipsilateral accessory oculomotor nuclei (50% in INC, 52.3% in NDK and 52% in NPC). In the 82.9% of cases, the responses were excitations, most of which having latencies and response characteristics compatible with a monosynaptic linkage. The remaining 17.1% of cases were inhibitions with latencies ranging between 4 and 11 ms. Extracellular field potential recordings within the accessory oculomotor nuclei were interpreted as arising from impulses propagating along excitatory axons projecting in a bundle from the cortex. Effects of exogenously applied excitatory amino acid N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (2APV) and of selective non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) were examined on synaptic excitation. Monosynaptic excitations induced by the cortical stimulation were abolished by microiontophoretic application of 2APV and not of DNQX. This finding indicates that cortical inputs activate specifically NMDA receptors of AON neurons.

c-fos expression in the accessory oculomotor nuclei following neocerebellar stimulation.

The present study was carried out to determine whether, in the rat, the electric activation of the projection from the cerebellar lateral nucleus (LN) to the accessory oculomotor nuclei (AON; nucleus of posterior commissure, nucleus of Darkschewitsch, interstitial nucleus of Cajal) is capable of inducing c-fos expression. In particular, we compared the effects of a continuous LN stimulation at low-frequency (tonic stimulation) with those induced by high frequency pulse trains (phasic stimulation). The observed results show that the stimulation of LN induces c-fos expression in a significant proportion of neurones in the contralateral AON. Phasic stimulation was slightly more effective than tonic stimulation in producing c-fos expression.

Effects of the retrorubral field stimulation on the excitability of the rat hippocampus in vivo.

We studied in vivo the influences exerted by the retrorubral field (RRF) on the on commissural-evoked CA1 pyramidal cell excitability in the rat hippocampal formation (HF). The stimulation of RRF before the activation of the contralateral CA3 area evoked in all the studied rats a reduction in amplitude of the evoked population spike in the CA1 pyramidal cell body layer of both the dorsal and the ventral HF. No significant differences in the intensity of the inhibitory effect were observed between dorsal and ventral parts of the HF. The stimulation of the ipsilateral RRF reduced the amplitude of the evoked population spike in a higher degree with respect to the contralateral side. Since these side-to-side differences were significant, it can be concluded that the RRF-induced inhibitory effect is stronger on the ipsilateral CA1 pyramidal cells. The inhibitory effect appears within 0.1 s of stimulating the RRF, reaches its maximal effect around 0.4-0.5 s following the conditioning train and returned to its control size after 5 s.

Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons.

The production of neurotrophin-4 (NT-4) in rat skeletal muscle was found to depend on muscle activity. The amounts of NT-4 messenger RNA present decreased after blockade of neuromuscular transmission with alpha-bungarotoxin and increased during postnatal development and after electrical stimulation in a dose-dependent manner. NT-4 immunoreactivity was detected in slow, type I muscle fibers. Intramuscular administration of NT-4 induced sprouting of intact adult motor nerves. Thus, muscle-derived NT-4 acted as an activity-dependent neurotrophic signal for growth and remodeling of adult motor neuron innervation. NT-4 may thus be partly responsible for the effects of exercise and electrical stimulation on neuromuscular performance.

The learning of novel finger movement sequences.

1. Experienced typists typed phrases containing words in which one isolated letter was typed with one hand, while the remaining letters were typed with the contralateral hand. 2. The translational and rotational motion of the fingers and wrist of the right hand were obtained optoelectronically from the location of reflective markers placed on the fingers. 3. Midway through the experiment, the key corresponding to the isolated letter was physically switched with another key on the keyboard, and subjects typed the letter in its new location (for 140 trials). The letter "n," typed with the right index finger, was either switched with letters normally typed with the same finger (u), with a different finger but same hand (o), with the same finger of the left hand (v), or with a different finger of the left hand (w). 4. When the words were typed normally, the interkey intervals were relatively short, and the onset of movement of the right hand began before the preceding keypress with the left hand. Thus the movement of the two hands overlapped. Furthermore, the movement to the isolated key was highly stereotypical, with little trial-to-trial variability. 5. After the transposition of keys, there were prolongations in the interkey intervals, with the largest delay occurring directly before the typing of the transposed key. Switches between homologous fingers (involving mirror movements) delayed the onset of keypresses to a lesser extent than did other switches. With practice, these delays were reduced but never reached the control level. 6. After the keyswitch, the onset of movement to the isolated key did not occur on average until after the last keypress with the contralateral hand, except when the switch involved the use of homologous fingers. In the latter case, overlapping movement of the two hands was maintained. Thus the learning of a series of discrete movements does not necessarily require that each movement segment be performed sequentially. 7. After the transposition of keys, the movement pattern and time course to a given key were similar to the movement patterns for that key observed during control trials in all conditions. Thus the learning of a series of movements may involve the use of previously learned movements under new conditions. 8. The results suggest that typing movements may be organized at several levels, including the individual keystroke and word level.

Non-N-methyl-D-aspartate receptors mediate neocerebellar excitation at accessory oculomotor nuclei synapses of the rat.

The nature of the receptor which mediates cerebellar-evoked monosynaptic excitations recorded from the accessory oculomotor nuclei (AON), i.e. the nucleus of posterior commissure, the nucleus of Darkschewitsch and the interstitial nucleus of Cajal, was studied in adult rats. Effects of exogenously applied excitatory amino acid (EAA) agonists N-methyl-D-aspartate (NMDA) and quisqualate (QUIS) and of selective NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (2APV) and non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) were examined on both amino acid induced and synaptic excitation. Microiontophoretic application of NMDA and QUIS in the AON of the rat increases the neuronal discharge in a dose-dependent manner. These findings suggest that in the rat cells belonging to AON bear both NMDA and non-NMDA receptors. This result was confirmed by the fact that applications of 2APV selectively antagonized NMDA-induced responses without affecting those to QUIS, while DNQX blocked specifically the excitatory responses to QUIS and did not affect NMDA-mediated excitations. We did not observe any difference, between rats anesthetized with urethane and those anesthetized with halothane, with respect to capability of EAA agonists NMDA and QUIS to increase the AON cells activity and of EAA receptor antagonists 2APV and DNQX to abolish the NMDA-induced and the QUIS-induced effects, respectively. In addition, monosynaptic excitations induced by the stimulation of cerebellar lateral nucleus were abolished by microiontophoretic application of DNQX, but not of 2APV. This finding indicates that neocerebellar inputs activate specifically non-NMDA receptors of AON neurons.

Effects of TRH-T on spinal motoneurones in man.

The effect of thyrotropin-releasing hormone tartrate (TRH-T) on the decrease in H Max/M Max ratio, an index of the spinal motoneurone pool, induced by haloperidol, was studied in 15 healthy volunteers. In all subjects, the H response was examined by an electromyographic apparatus. The values were expressed as H Max/M Max ratio, that gives an index of excitability of the spinal motoneurone pool. It was found that the mean H Max/M Max ratio value significantly decreased after haloperidol administration, but this effect was completely reversed by the injection of TRH-T. This finding suggests that the peptide may modulate motoneurone functions.

Unilateral enhancement of early and late blink reflex components in hemidystonia.

The side-to-side differences in the EMG activity of the early and late components of blink reflex, regarded as revealing the state of excitability of the brain stem reflex centers, have been analyzed in patients with unilateral dystonia without demonstrable brain lesions. It has been observed that both early and late responses of direct blink reflex were higher on the side affected by hemidystonia than on the contralateral one, while the latency values were in the normal range. Possibility that an abnormal output from the striatum towards the brainstem structures involved in blink reflex appears on the affected side of hemidystonic patients is discussed.