P. Andre

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.

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.

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.

RESPONSES OF PURKINJE CELLS IN THE CEREBELLAR ANTERIOR VERMIS TO OFF-VERTICAL AXIS ROTATION

Responses of 67 Purkinje cells (P-cells) and 44 unidentified neurons (U-cells) located in the cerebellar anterior vermis were recorded in decerebrate cats during off-vertical axis rotation (OVAR). This stimulus consisted of a slow constant velocity (9.4°/s) rotation in the clockwise (CW) and counterclockwise (CCW) directions around an axis inclined by 5° with respect to the vertical. OVAR imposes on the animal head a 5° tilt, whose direction changes continuously over the horizontal plane, thus eliciting a selective stimulation of macular receptors. A total of 27/67 P-cells (40%) and 24/44 U-cells (55%) responded to both CW and CCW rotations. For these bidirectional units, the direction of maximum sensitivity to tilt (Smax) could be identified. Smax directions were distributed over the whole horizontal plane of stimulation. Among bidirectional neurons, 48% of the P-cells and 33% of the U-cells displayed an equal amplitude of modulation during CW and CCW rotations, indicating a cosinetuned behaviour. In these instances, the temporal phase of the unit response to a given direction of tilt remained constant, while the sensitivity was maximal along the Smax direction and declined with the cosine of the angle between Smax and the tilt direction. The remaining bidirectional units displayed unequal amplitudes of modulation during CW and CCW rotations. For these neurons, a nonzero sensitivity along the null direction was expected and the response phase varied as a function of stimulus direction. Finally, 31% and 23% of P-cells and U-cells, respectively, responded during OVAR in one direction only (unidirectional units). This behaviour predicts equal sensitivities along any tilt direction in the horizontal plane and a response phase that changes linearly with the stimulus direction. The possibility that the tested neurons formed a population which coded the direction of head tilt in space was also investigated. The data from the whole population of cells were analysed using a modified version of vectorial analysis. This model assumes that for a particular tilt each cell makes vectorial contributions; the vectorial sum of these contributions represent the outcome of the population code and points in the direction of head tilt in space. Thus, a dynamic head tilt along four representative directions was simulated. For each of the four directions, 12 population vectors were calculated at regular time intervals so as to cover an entire cycle of head tilt. The results indicate that for each selected time in the cycle the direction of the population vector closely corresponded to that of the head tilt, while its amplitude was related to the amount of head tilt. These data were particularly obtained for the P-cells. In view of their efferent connections, the cerebellar anterior vermis may provide a framework for the spatial organization of vestibulospinal reflexes induced by stimulation of otolith receptors.

Activation of muscarinic receptors induces a long-lasting enhancement of Purkinje cell responses to glutamate

The cerebellar cortex contains diffusely distributed cholinergic fibers and both muscarinic and nicotinic receptors. Behavioral studies suggest that an important function of this cholinergic innervation may be to modulate the effects of afferent input to the cerebellar cortex. The present study compared the effects of the muscarinic agonist bethanechol on basal firing rates and on glutamate-evoked firing of Purkinje cells in the vermis of the cerebellum of anesthetized rats. Microiontophoretic application of bethanechol produced a slowly developing, long-lasting enhancement of glutamate-evoked firing which was often disassociated from the bethanechol effect on the basal firing rate. Bethanechol increased the glutamate response of 22/33 Purkinje cells regardless of whether bethanechol increased, decreased or failed to alter the basal firing rate of the cell. The muscarinic antagonist scopolamine prevented the bethanechol-induced increase in the glutamate response. For 7/33 Purkinje cells, bethanechol decreased the glutamate-evoked response. However, this decrease did not appear to be mediated by muscarinic receptors because it was not blocked by scopolamine and it was mimicked by application of the vehicle alone. Acetylcholine application produced a long-lasting increase in the glutamate response of 4/5 Purkinje cells that was similar to the bethanechol effect. These data indicate that the cerebellar cholinergic system exerts a prominent modulatory influence on Purkinje cell excitability by acting through muscarinic receptors.

NECK INFLUENCES ON THE SPATIAL PROPERTIES OF VESTIBULOSPINAL REFLEXES IN DECEREBRATE CATS: ROLE OF THE CEREBELLAR ANTERIOR VERMIS

The vestibulospinal (VS) reflexes elicited by animal rotation modify the activity of limb musculature, thus preserving balance and postural stability. We investigated whether the orientation of these postural responses is strictly dependent upon the direction of head displacement or else can be modified by extralabyrinthine inputs to the goal of stabilizing body position. The experiments were performed in decerebrate cats, in which the effects of static body-to-head displacements were tested on the multiunit EMG responses of the medial head of the triceps brachii to wobble of the whole animal at 0.15 Hz, 10 degrees, both in the clockwise (CW) and counterclockwise (CCW) direction. These stimuli allowed us to determine the muscle response vector, whose orientation component corresponds to the direction of head displacement giving rise to the maximal EMG response. When the animal body was kept straight with respect to the head, the triceps response vector was always oriented close to the transverse axis, pointing to the side-down direction. Following 30 degrees of body-to-head displacement around a vertical axis passing through the first-second cervical joints, the response vectors of both the left and the right muscles shifted in the same direction of body rotation, thus remaining approximately perpendicular to the body axis. The change in muscle vector orientation corresponded on the average to the angle of body-to-head displacement. Only slight changes in amplitude of the muscle responses were observed. These findings imply that the maximal activation of the triceps brachii always occurred for the same direction of body displacement, irrespective of the pattern of discharge of vestibular afferents, which is determined by the direction of head displacement. The rotation of the triceps response vector induced by body-to-head displacement was reduced or suppressed by inactivation of the ipsilateral cerebellar anterior vermis, following local microinjection of the GABA(A) agonist muscimol. These findings indicate that 1) the sensory input which results from changing the body position with respect to the head, probably originating from neck receptors, is able to modify the pattern of the VS reflexes, which appear to be organized in a body-centered reference frame, and 2) the cerebellar vermis is required for the proper execution of this sensorimotor transformation.

The muscarinic agonist, bethanechol, enhances GABA-induced inhibition of purkinje cells in the cerebellar cortex

An important function of cholinergic projections to the cerebellar cortex may be to modulate the effects of classical afferent inputs to the cerebellar cortex. This hypothesis is supported by the recent observation that cholinergic agonists act at muscarinic receptors in the cerebellar cortex to facilitate Purkinje cell responses to glutamate, the excitatory neurotransmitter of parallel fibers [Brain Res., 617 (1993) 28-36]. Since Purkinje cell excitability is influenced by inhibitory input from basket and stellate cells as well as by excitatory input from granule cells and climbing fibers, the present study investigated whether muscarinic agonists could also modify the Purkinje cell responses to GABA, the putative inhibitory transmitter of basket and stellate neurons. In anesthetized rats, microiontophoretic application of bethanechol produced a long-lasting enhancement of GABA-evoked inhibition of firing of Purkinje cells in the cerebellar vermis (22/25 cells) regardless of whether bethanechol increased, decreased or failed to alter the basal firing rate of the cell. The muscarinic antagonist scopolamine prevented the bethanechol-induced increase in the GABA response. It appears, therefore, that cholinergic activation of muscarinic receptors enhances not only the excitatory but also the inhibitory component of cerebellar cortex circuitry. Further experiments are required to investigate whether this combination of effects may potentiate the signal processing capabilities of the cerebellar cortex.

Blink-related delta oscillations in the resting-state EEG: A wavelet analysis

Over the past decades, many studies have linked the variations in frequency of spontaneous blinking with certain aspects of information processing and in particular with attention and working memory functions. On the other hand, according to the theory postulated by Crick and Koch, the actual function of primary consciousness is based on the reciprocal interaction between attention and working memory in the automatic and serial mode. The purpose of this study was to investigate for electrophysiological correlates compatible with the cognitive nature of spontaneous blinking, by using the EEG recordings obtained in a group of seven healthy volunteers while they rested quietly though awake, with their eyes open, but not actively engaged in attention-demanding goal-directed behaviours. The global wavelet analysis - at total of 189 three-second EEG epochs time-locked to the blink - revealed an increase in the delta band signal corresponding to the blink. In particular, a reconstruction of the EEG signal by means of inverse-wavelet transform (IWT) showed a blink-related P300-like wave at mid-parietal site. We assumed this phenomenon to represent an electrophysiological sign of the automatic processing of contextual environmental information. This might play a role in maintaining perceptive awareness of the environment at a low level of processing, while the subject is not engaged in attention-demanding tasks but rather introspectively oriented mental activities or free association(s).

Adaptive modification of the cat's vestibulospinal reflex during sustained and combined roll tilt of the whole animal and forepaw rotation : Cerebellar mechanisms

In decerebrate cats, the electromyogram (EMG) activity of the forelimb extensor triceps brachii (TB) increases during side-down roll tilt of the whole animal (vestibulospinal reflex, VSR) at about 0.15 Hz. (+/-10 degrees ), while decreases during side up tilt. On the other hand, the TB activity increases during dorsal flexion of the ipsilateral forepaw (0.15 Hz, +/-5 degrees-10 degrees ), but decreases during ventral flexion. In six experiments, these stimuli were synergistically associated (side-down tilt coincided with dorsal flexion of the forepaw), so that the EMG modulation of the TB activity was greater than that induced by the individual stimuli. During a 3-h period of this sustained stimulation, the amplitude of the pure VSR progressively increased to reach the maximum value at the end of the third hour and persisted unmodified during the post-adaptation period (1 h). In three experiments, animal tilt and forepaw rotation were antagonistically associated (side-down tilt coincided with ventral flexion of the forepaw). In these instances the VSR gain remained on the average stable, but, at the end of the 3-h period of combined stimulation, a proportion of TB responses to animal tilt showed a phase reversal. In a digitigrade animal like the cat, a dorsal flexion of the wrist is associated with a decrease in limb length and would occur when the extensor tone is not appropriate to support body weight; we propose, therefore, that somatosensory volleys elicited by wrist rotation modify the gain of VSR so as to maintain postural stability. Inactivation, on the side of muscle recording, of the corticocerebellar region which projects to the lateral vestibular nucleus of Deiters, by local microinjection of the GABA-A agonist muscimol (0.5 microl at 16 microg/microl), decreased the already adapted gain of VSR. In conclusion, the results of this study suggest that somatosensory reafferent inputs to the cerebellar vermis are used to plastically modify the gain of VSR, when external forces produce changes in the final posture of the foot during animal tilt.

Noradrenergic agents into the cerebellar anterior vermis modify the gain of vestibulospinal reflexes in the cat

The noradrenergic (NA) afferent projection to the cerebellar cortex, which originates mainly from the locus coeruleus (LC), may act on the target neurons by utilizing both alpha- and beta-adrenoceptors. Experiments performed in decerebrate cats have shown that unilateral injection into the vermal cortex of the cerebellar anterior lobe of 0.25 microliter of the alpha 1-adrenergic agonist metoxamine or the alpha 2-agonist clonidine (at 2-8 micrograms/microliters of saline) as well as of the non-selective beta-agonist isoproterenol (at 8-16 micrograms/microliters) decreased the postural activity in the ipsilateral forelimb, while the extensor tonus either remained unmodified or slightly increased on the contralateral side. The same agents also increased the gain of the vestibulospinal (VS) reflexes elicited by recording the multiunit EMG responses of the ipsilateral and the contralateral triceps brachii to roll tilt of the animal (at 0.15 Hz, +/- 10 degrees), leading to sinusoidal stimulation of labyrinth receptors. The crossed effects were more prominent for the alpha 2- than for the alpha 1- and beta-agonists. Only slight changes in the phase angle of the responses were observed. The effects described above appeared 5-10 min after the injection, reached the peak values after 15-30 min and disappeared within 2 h. The effective area was located within the third and/or the fourth folium of the culmen rostral to the fissura prima, 1.4-1.8 mm lateral to the midline. This area corresponded to zone B of the cerebellar cortex, which projects to the ipsilateral lateral vestibular nucleus (LVN), on which it exerts a prominent inhibitory influence. In fact, monopolar stimulation of this area with three negative pulses (at 300/sec) performed prior to the local injection inhibited the spontaneous EMG activity of the ipsilateral triceps brachii. The effects described above were dose-dependent; injection of an equal volume of saline was ineffective. All changes in posture and reflexes elicited by metoxamine or clonidine were impaired by previous injection into the same corticocerebellar area of the corresponding alpha 1- or alpha 2-adrenergic antagonist prazosin or yohimbine, respectively (0.25 microliters at 8-16 micrograms/microliters). However, cross-interactions between alpha 1- and alpha 2-adrenergic agonists and antagonists were also observed. In fact, injection of the alpha 2-adrenergic antagonist yohimbine prevented the occurrence of all the metoxamine effects, while administration of the alpha 1-adrenergic antagonist prazosin prevented the occurrence of the ipsilateral, but not of the contralateral effects induced by clonidine injection.(ABSTRACT TRUNCATED AT 400 WORDS)