Diego Manzoni

Locus coeruleus control of spinal motor output

Using electrophysiological techniques, we investigated the functional properties of the coeruleospinal system for regulating the somatomotor outflow at lumbar cord levels. Many of the fast-conducting, antidromically activated coeruleospinal units were shown to exhibit the alpha 2-receptor response common to noradrenergic locus coeruleus (LC) neurons. Electrically activating the coeruleospinal system potentiated the lumbar monosynaptic reflex and depolarized hindlimb flexor and extensor motoneurons via an alpha 1-receptor mechanism. The latter synaptically induced membrane depolarization was mimicked by norepinephrine applied iontophoretically to motoneurons. That LC inhibited Renshaw cell activity and induced a positive dorsal root potential at the lumbar cord also reinforced LCs action on motor excitation. We conclude that LC augments the somatomotor output, at least in part, via an alpha 1-adrenoceptor-mediated excitation of ventral horn motoneurons. Such process is being strengthened by LCs suppression of the recurrent inhibition pathway as well as by its presynaptic facilitation of afferent impulse transmission at the spinal cord level.

The cerebellum and sensorimotor coupling: looking at the problem from the perspective of vestibular reflexes.

Cerebellar modules process afferent information and deliver outputs relevant for both reflex and voluntary movements. The response of cerebellar modules to a given input depends on the whole array of signals impinging on them. Studies on vestibular reflexes indicate that the response of the cerebellar circuits to the vestibular input is modified by the integration of multiple visual, vestibular and somatosensory afferent signals. In this way the cerebellum slowly adapts these reflexes when they are not adequate to the behavioural condition and allows their fast modifications when the relative position of the body segments and that of the body in space are changed. Studies on voluntary movements indicate that the cerebellum is responsible for motor learning that consists of the development of new input-output associations. Several theoretical, anatomical and clinical studies are consistent with the hypothesis that the cerebellum allows the delivery of motor commands which vary according to the condition of the motor apparatus. Finally, the cerebellum could change the relation between visual information and aimed reaching movements according to the position of the eyes in the orbit and of the neck over the body. We propose that, due to the large expansion of its cortex, an important function of the cerebellum could be that of expanding the range of sensorimotor associations according to all the factors characterizing the behavioural condition. Indeed, following cerebellar lesion, learning is often lost, the movement results impaired and requires an increased attention. In the light of the recently discovered connections of the cerebellum with the rostral regions of the frontal lobe, it can be suggested that the ability of cerebellar circuits to modify the rules of input-output coupling according to a general context is a fundamental property allowing the cerebellum to control not only motor but also cognitive functions.

The cerebellum may implement the appropriate coupling of sensory inputs and motor responses: evidence from vestibular physiology.

Starting from a survey of current ideas on the role of the cerebellum in sensorimotor transformations, the present review summarizes the results of recent experiments showing that (a) somatosensory signals modify the spatial organization of the postural reflexes, thus leading to body stability, and (b) otolith input changes the plane of reflex eye movements, by keeping it perpendicular to the gravito-inertial vector. Evidence will be given that both transformations require the integrity of specific cerebellar regions. These data indicates that the cerebellum allows an optimal input-output coupling in relation to the ultimate behavioural goal of the motor activity.

Responses of locus coeruleus and subcoeruleus neurons to sinusoidal stimulation of labyrinth receptors

In precollicular decerebrate cats the electrical activity of 141 individual neurons located in the locus coeruleus-complex, i.e. in the dorsal (n = 41) and ventral parts (n = 67) as well as in the locus subcoeruleus (n = 33), was recorded during sinusoidal tilt about the longitudinal axis of the whole animal, leading to stimulation of labyrinth receptors. Some of these neurons showed physiological characteristics attributed to the norepinephrine-containing locus coeruleus neurons, namely, (i) a slow and regular resting discharge, and (ii) a typical biphasic response to fore- and hindpaw compression consisting of short impulse bursts followed by a silent period, which has been attributed to recurrent and/or lateral inhibition of the norepinephrine-containing neurons. Furthermore, 16 out of the 141 neurons were activated antidromically by stimulation of the spinal cord at T12 and L1, thus being considered coeruleospinal or subcoeruleospinal neurons. A large number of tested neurons (80 out of 141, i.e. 56.7%) responded to animal rotation at the standard frequency of 0.15 Hz and at the peak amplitude of 10 degrees. However, the proportion of responsive neurons was higher in the locus subcoeruleus (72.7%) and the dorsal locus coeruleus (61.0%) than in the ventral locus coeruleus (46.3%). A periodic modulation of firing rate of the units was observed during the sinusoidal stimulus. In particular, 45 out of the 80 units (i.e. 56.2%) were excited during side-up and depressed during side-down tilt (beta-responses), whereas 20 of 80 units (i.e. 25.0%) showed the opposite behavior (alpha-responses). In both instances, the response peak occurred with an average phase lead of about + 18 degrees, with respect to the extreme side-up or side-down position of the animal; however, the response gain (imp./s per deg) was, on average, more than two-fold higher in the former than in the latter group. The remaining 15 units (i.e. 18.7%) showed a prominent phase shift of this response peak with respect to animal position. Similar results were obtained from the subpopulation of locus coeruleus-complex neurons which fired at a low rate (less than 5.0 imp./s), as well as for the antidromically identified coeruleospinal neurons. The response gain of locus coeruleus-complex neurons, including the coeruleospinal neurons, did not change when the peak amplitude of tilt was increased from 5 degrees to 20 degrees at the fixed frequency of 0.15 Hz. This indicates that the system was relatively linear with respect to the amplitude of displacement.(ABSTRACT TRUNCATED AT 400 WORDS)

Neck input modifies the reference frame for coding labyrinthine signals in the cerebellar vermis : A cellular analysis

The activity of 68 neurons, mainly Purkinje cells, was recorded from the cerebellar anterior vermis of decerebrate cats during wobble of the whole animal (at 0.156 Hz, 5 degrees), a mixture of tilt and rotation, leading to stimulation of labyrinth receptors. Most of the neurons (65/68) were affected by both clockwise and counterclockwise rotations. Twenty-four units showing responses of comparable amplitude to these stimuli (narrowly tuned cells) were represented by a single vector (Smax), whose preferred direction corresponded to the direction of stimulation giving rise to the maximal response. The remaining 41 units, however, showed different amplitude responses to these rotations (broadly tuned cells) and were characterized by two spatially and temporally orthogonal vectors (Smax and Smin), suggesting that labyrinthine signals with different spatial and temporal properties converged on these cells. All these units were tested while the body was aligned with the head (control position), as well as after static displacement of the body under a fixed head by 15 degrees and/or 30 degrees around a vertical axis passing through C1-C2, thus leading to stimulation of neck receptors. The orientation component of the response vector of the Purkinje cells to vestibular stimulation changed following body-to-head displacement. Moreover, the amplitude of vector rotation corresponded, on the average, to that of body rotation. Changes in temporal phase, gain and tuning ratio of the responses were also observed. We propose that information from neck receptors regulates the convergence of labyrinthine signals with different spatial and temporal properties on corticocerebellar units. Due to their strict relationship with the motor system, these units may give rise to appropriate responses in the limb musculature, by modifying the spatial organization of the vestibulospinal reflexes according to the requirements of body stability. The cerebellar vermis may thus represent an important structure, where frames of reference can be altered to account for changes in position of trunk, head and neck.

Effects of stimulation of vestibular and neck receptors on Deiters neurons projecting to the lumbosacral cord

Abstract1. The activity of lateral vestibular nucleus (LVN) neurons, antidromically identified by stimulation of the spinal cord at T12 and L1, thus projecting to the lumbosacral segments of the spinal cord (lVS neurons), was recorded in precollicular decerebrate cats during rotation about the longitudinal axis either of the whole animal (labyrinth input) or of the body only while the head was kept stationary (neck input). 2. Among the lVS neurons tested for vestibular stimulation, 76 of 129 units (i.e. 58.9%) responded to roll tilt of the animal at the standard parameters of 0.026 Hz, ±10°. The gain and the sensitivity of the first harmonic responses corresponded on the average to 0.47±0.44, SD, impulses·s−1·deg−1 and 3.24±3.15, SD, %/deg, respectively. As to the response patterns, 51 of 76 units (i.e. 67.1%) were excited during side-down and depressed during side-up tilt, whereas 15 (i.e. 19.7%) showed the opposite behavior. In both instances the peak of the responses occurred with an average phase lead of about +21.0±27.2., SD, deg with respect to the extreme side-down or side-up position of the animal. Moreover, the former group of units showed almost a twofold larger gain with respect to the latter group (t-test,p<0.05). 3. Among the lVS neurons tested for neck stimulation, 75 of 109 units (68.8%) responded to neck rotation at the standard parameters. The gain and the sensitivity of the first harmonic responses corresponded on the average to 0.49±0.40, SD, impulses·s−1·deg−1 and 3.30±3.42, SD, %/deg, respectively, thus being similar to the values obtained for the labyrinth responses. However, 59 of 75 units (i.e. 78.6%) were excited during side-up neck rotation and depressed during side-down neck rotation, while 8 of 75 units (i.e. 10.7%) showed the opposite pattern. In both instances the peak of the responses occurred with an average phase lead of +52.0±18.3, SD, deg for the extreme side-up or side-down neck displacements. Further, the former group of units showed a larger gain than the latter group. 4. Histological controls indicated that 102 of 129 (i.e. 79.0%) lVS neurons tested for labyrinth stimulation and 86 of 109 (i.e. 78.9%) lVS neurons tested for neck stimulation were located in the dorsocaudal part of LVN, the remaining lVS neurons being located in the rostroventral part of LVN. 5. The observation that the predominant response pattern of the lVS neurons to roll tilt was just opposite to that of lVS neurons to neck rotation indicates that the motoneurons innervating ipsilateral hindlimb extensors were excited by an increased discharge of vestibulospinal neurons during side-down tilt but they were disfacilitated by the reduced discharge of vestibulospinal neurons during side-down neck rotation; the opposite would occur during side-up animal tilt or neck rotation. These findings were compared with those of previously recorded LVN neurons, whose descending axons were not identified as projecting to upper or lower segments of the spinal cord. It was then possible to evaluate the role that the LVN exerts not only in the control of the limb but also of the neck extensor musculature.

Spatiotemporal response properties of cerebellar Purkinje cells to animal displacement: a population analysis

The hypothesis that corticocerebellar units projecting to vestibulospinal neurons contribute to the spatiotemporal response characteristics of forelimb extensors to animal displacement was tested in decerebrate cats in which the activity of Purkinje cells and unidentified cells located in the cerebellar anterior vermis was recorded during wobble of the whole animal. This stimulus imposed to the animal a tilt of fixed amplitude (5 degrees) with a direction moving at a constant angular velocity (56.2 degrees/s), both in the clockwise and counterclockwise directions over the horizontal plane. Eighty-three percent (143/173) of Purkinje cells and 81% (42/52) of unidentified cells responded to clockwise and/or counterclockwise rotations. In particular, 116/143 Purkinje cells (81%) and 32/42 unidentified cells (76%) responded to both clockwise and counterclockwise rotations (bidirectional units), while 27/143 Purkinje cells (19%) and 10/42 unidentified cells (24%) responded to wobble in one direction only (unidirectional units). For the bidirectional units, the direction of maximum sensitivity to tilt (Smax) was identified. Among these units, 24% of the Purkinje cells and 26% of the unidentified cells displayed an equal amplitude of modulation during clockwise and counterclockwise rotations, indicating a cosine-tuned behavior. For this unit type, the temporal phase of the response to a given direction of tilt should remain constant, while the sensitivity would be maximal along the Smax direction, declining with the cosine of the angle between Smax and the tilt direction. The remaining bidirectional units, i.e. 57% of the Purkinje cells and 50% of the unidentified cells displayed unequal amplitudes of modulation during clockwise and counterclockwise rotations. For these neurons, a non-zero sensitivity along the null direction is expected, with a response phase varying as a function of stimulus direction. As to the unidirectional units, their responses to wobble in one direction predict equal sensitivities along any tilt direction in the horizontal plane and a response phase that changes linearly with the stimulus direction. By comparing these data with those obtained previously during selective stimulation of macular receptors by a 5 degrees off-vertical axis rotation, it appeared that the directions of maximum sensitivity to tilt were distributed over the whole horizontal plane of stimulation, in both conditions. However, co-stimulation of macular and canal receptors during wobble decreased the proportion of unidirectional units, while that of the bidirectional, namely broadly tuned units, increased. In addition, while the average gain of the Smax vector of the bidirectional units was comparable, the temporal phase of this vector tended to show a more prominent phase leading behavior during wobble with respect to off-vertical axis rotation. The possibility that the tested neurons formed a population which coded the direction of head tilt in space was also investigated using a modified version of the classical population vector analysis. It was shown that for each selected time in the tilt cycle the direction of the population vector closely corresponded to that of the head tilt, while its amplitude was related to that of the stimulus. We conclude that the broad distribution of the response vector orientation of units located in the cerebellar anterior vermis represents an appropriate substrate for the cerebellar control of vestibulospinal reflexes involving extensor muscles during a variety of head tilts. In view of their efferent projections to the vestibular and fastigial nuclei, the cerebellar anterior vermis may provide a framework for the spatial coding of vestibular inputs, giving equal emphasis to both side-to-side and fore-aft stability.

Hypnotizability-related integration of perception and action

Hypnotizability is a cognitive trait able to modulate many behavioural/physiological processes and associated with peculiar functional characteristics of the frontal executive system. This review summarizes experimental results on hypnotizability-related differences in sensorimotor integration at a reflex and an integrated level (postural control) and suggests possible interpretations based on morpho-functional considerations. In particular, hypnotizability-related differences in spinal motoneurones excitability are described, and the role of attention and imagery in maintaining a stable upright stance when sensory information is reduced or altered and when attention is absorbed in cognitive tasks is discussed as a function of hypnotic susceptibility. The projections from prefrontal cortex to spinal motoneurones and the balance between the activation of the right and left cortical hemisphere are considered responsible for the hypnotizability-related modulation of reflex responses, while the differences in postural control between subjects with high (highs) and low (lows) hypnotic susceptibility are considered a possible consequence of the activity of the locus coeruleus, which is also involved in attention, and of the cerebellum, which might be responsible for different internal models of postural control. We suggest a highly pervasive role of hypnotic susceptibility in human behaviour through the modulation of the integration of perception and action, which could be relevant for neurorehabilitative treatments and for the adaptation to special environments.

Hypnotizability-dependent modulation of postural control: effects of alteration of the visual and leg proprioceptive inputs.

The aim of the experiment was to investigate whether the peculiar attentional/imagery abilities associated with susceptibility to hypnosis might make postural control in highly hypnotizable subjects (Highs) that are less vulnerable to sensory alteration than in individuals with low hypnotic susceptibility (Lows). The movement of the centre of pression (CoP) was monitored in Highs and Lows during alteration of the visual and leg proprioceptive input. The two groups responded differently to eyes closure and to an unstable support and the CoP movement was generally larger and faster in Highs. The stabilogram diffusion analysis indicated a different set point in Highs and Lows and suggested that the former are more independent of specific sensory information than the latter, likely due to different abilities in sensory re-weighting and/or peculiar internal models of postural control. The results are discussed within the general perspective of high pervasiveness of the hypnotizability trait, which modulates cognitive, autonomic and somatic functions.

The relation between EMG activity and kinematic parameters strongly supports a role of the action tremor in parkinsonian bradykinesia

The kinematics characteristics of an upper arm extension of large amplitude (90°) performed in the horizontal plane and the simultaneous activity of the shoulder muscles were recorded in 12 parkinsonian patients and in six normal control subjects. The movement, triggered by an acoustic “go” signal, was preceded by an isometric adduction.