1,721,013 research outputs found
Modulation of Purkinje cell response to glutamate during the sleep-waking cycle.
No full textAbstract
The hypothesis that corticocerebellar responsiveness is modified by the behavioral state was tested in freely moving rats by evaluating the responses of extracellularly recorded Purkinje cells located in the cerebellar posterior vermis to microiontophoretically applied glutamate (8-80 nA for 3-5 s every 30-32 s) during the spontaneous sleep-waking cycle. Rats were chronically implanted for polygraphic recordings so that responses of Purkinje cells to glutamate could be related to the states of quiet waking, slow-wave sleep and paradoxical sleep. Analysis on a population of 33 neurons subjected to alternate periods of sleep and waking showed that the mean response to glutamate was significantly reduced to 75 ± 18% during slow-wave sleep with respect to waking. This effect occurred independently on changes of basal firing rate which in sleep was slightly, although significantly, reduced to 94 ± 12%. Independence of glutamate response modulation from changes of baseline firing was also observed in a different data set obtained from 19 Purkinje cells which were recorded during a continuous slow-wave sleep period that allowed several consecutive drug applications. In this condition responses to glutamate progressively decreased as sleep proceeded while spontaneous activity remained stable after a slight decrease at the transition from waking to sleep. Spectral analysis performed on the electroencephalogram signal, in particular on epochs centered around each glutamate pulse, revealed that for both data sets the reduction of neuronal responsiveness was related to the intensity of slow-wave sleep and more precisely to the delta and slow oscillation (0.6-4.2 Hz) content of the power spectrum of the electroencephalogram. Spontaneous and glutamate-evoked activity were also evaluated in 23 Purkinje cells during transition from slow-wave sleep to paradoxical sleep. In particular, during paradoxical sleep spontaneous activity became irregular so that for 44 out of 90 glutamate responses quantification was unreliable. The remaining 46 responses were characterized by high variability in amplitude even within the same episode of paradoxical sleep. With respect to the preceding slow-wave sleep values, 17/46 responses increased, 14/46 decreased and 15/46 remained within the 15% limit, giving a mean value of 132%. These data indicate that Purkinje cell response to glutamate is modulated during the spontaneous sleep-waking cycle. We speculate that this modulation depends upon the action of the neuromodulatory systems which diffusely project to the cerebellum, whose function would be to adapt the performance of the cerebellar circuits to changes of the animal state. On the other hand, the phasic changes in amplitude of Purkinje cell response during paradoxical sleep could be due to the interaction between the effects of glutamate application and those exerted by endogenous signals possibly related to the phasic events of this sleep stage
Hipnic modulation of cerebellar information processing: implications for the cerebro-cerebellar dialogue
No full textRecent evidence indicates that during the sleep-waking cycle the forebrain and the cerebellum show parallel changes of their operating capabilities and suggest that cooperation between these two structures plays a different role in the different behavioral states. In particular, a high degree of cerebro-cerebellar cooperation is expected in waking and in paradoxical sleep when enhanced information processing within the cerebellum and the cortex is associated with effective reciprocal cerebro-cerebellar signal transmission. We first speculate that during waking, a state in which a wide range of behaviors is produced by the interaction with the external world, the cerebellum might assist the cortex to develop the neural dynamic patterns which underlie behaviors and that this could be accomplished via cerebellar modulation of both short- and long-range cortical synchronization. In particular, we propose that the cerebellum might favour the automatic triggering of the patterns already acquired, when requested by the context, as well as the acquisition of novel patterns, when found to be of adaptive value, and might even modulate the access to consciousness of brain operations, if producing unpredicted results, by regulating pattern complexity. This proposal is based on the experimental evidence that oscillatory activity may flow within the cerebro-cerebellar loops and that stimulation or lesion of the cerebellar structures affects cortical synchronization. Then we report evidence indicating that during paradoxical sleep, when brain activation occurs in the absence of sensory inflow and motor output, cerebro-cerebellar cooperation mainly favours consolidation of newly acquired waking patterns and/or savings of old patterns from disruption possibly through a non-utilitarian replay process. Finally, we propose that cerebro-cerebellar cooperation weakens during slow wave sleep, given that in this sleep state neuronal activity and excitability decrease both in the cerebellum and in the forebrain and cerebello-cortical signal transmission is at least partially gated at the thalamic level
Rapporti fra cervelletto e stati di vigilanza. Medicina del Sonno, Bollettino A.I.M.S., 1: 2-8, 2000
No full textExperimental evidences are reported on the relationship between the cerebellum and the behavioural states. The available data do not support an executive role for the cerebellum in the generation of the sleep-waking rhythm since partial or total cerebellar lesions do not consistently affect the time spent in sleep and waking. In stead, they indicate that cerebellar activity may exert a relevant modulatory control on both the EEG rhythms and patterns. The hypothesis that the cerebellum may regulate cortical activation arises from experiments of cerebellar stimulation or lesion leading to synchronisation/desynchronisation of the EEG. In particular , two cerebellothalamocortical systems have been postulated, one channel arising in the lateral cerebellum (hemispheres, inter positus and dentate nuclei) projecting to discrete cortical fields, the other channel arising in the medial cerebellum (vermal cortex and fastigial nu- cleus) projecting to widespread cortical areas mainly through intralaminar non-specific thalamic nuclei. While the first channel may be involved in specific motor and non-motor functions, the second one may diffusely affect cortical activation and provide a mechanism for cerebellar control of cortical processing depending on the context and on behavioural states. Interestingly , fastigial stimulation not only blocks the slow EEG waves and causes arousal, but also induces fast activity at 40 Hz coherent in multiple cortical foci, a finding of interest in the light of the hypothesis that transient synchronous activity of functionally specialised groups of neurons located in different cortical sites and oscillating around 40 Hz may stay at the basis of cognitive experience. Next, we review the effects of the vigilance states on the activity and excitability of the cerebellar neurons. Results of neuronal recordings, measurement of regional blood flow/metabolism and detection of immediate-early gene expression all converge in indicating that during waking and paradoxical sleep cerebellar activity is higher than during slow wave sleep. Moreover , recent microiontophoretic data showed that Purkinje cell responsiveness is enhanced during the activated states (waking and paradoxical sleep) and depressed during slow wave sleep, suggesting that the signal processing capabilities within the cerebellar cortex are also affected by the behavioral state. We speculate that higher excitability might enhance the information transfer which is required within the cerebellar circuits during waking, while a lower degree of neuronal responsiveness during slow wave sleep could fulfil the necessity to develop restorative processes in this state. Finally relatively high responsiveness is ob served during paradoxical sleep when sensory input and motor output are both inhibited but a state of intense tonic and phasic central activation is generated within the brain
Effects of locus coeruleus stimulation on the responses of SI neurons of the rat to controlled natural and electrical stimulation of the skin.
No full textAbstract
1. The effects of microstimulation of the locus coeruleus (LC) region on the spontaneous discharge and the response of SI neurons to natural and electrical stimulation of the skin have been investigated in 26 urethane anesthetized Sprague-Dawley rats. In particular, one or two air puffs, 5-10 msec in duration, 1-2 psi, usually separated by an interval of 40 msec, were applied on the hairy skin of the wrist or the forepaw at the presentation rate of 1/sec. For units unresponsive to air puffs, similar presentation of low intensity electrical stimuli (0.2-5.0 V, 0.2-0.4 msec pulses) were applied through two needles inserted on the most effective area of the skin. Both natural and electrical stimulations of the skin were applied under control conditions, as well as 50 msec after a 250 msec train of 0.3 msec pulses at 40 Hz, 20-30 μA applied stereotaxically to the LC complex through a tungsten microelectrode. 2. Not all cortical units exhibited spontaneous discharge. Most of the units, however, which were spontaneously active, were inhibited by electrical stimulation of the LC complex, while the remaining ones were excited. The sites of stimulation, which included either the LC proper or the locus subcoeruleus, were identified following both anatomical and physiological criteria. 3. SI neurons recorded at sites between 400 and 950 μm below the surface of the cortex, thus being most likely granule cells of layers III and IV, responded to cutaneous stimuli with spikes which occurred with a latency of 20-30 msec in response to single air puffs and a latency of 15-20 msec in response to single electrical pulses to the skin. In both instances the response to the second stimulus applied at the interstimulus interval of 40 msec was markedly reduced or abolished due to postexcitatory inhibition following the response to the first stimulus (in- field inhibition). In contrast, units particularly located at or below 1000 μm from the cortical surface, which were of very large size probably corresponding to large layer V pyramidal cells, were often difficult to activate with air puffs applied at the centre of the receptive field (RF) and were submitted to electrical stimulation of the skin. 4. Among the 59 isolated SI units tested either to air puffs (45 neurons) or to electrical skin stimulation (14 neurons), 15 units (i.e., 25.4%) were facilitated, while 12 units (i.e., 20.3%) were inhibited following stimulation of the LC complex. 5. A marked feature of the facilitatory effects which usually involved the predominant response to the first air puff, but also the smaller response to the second puff, was that the increase in the number of spikes per stimulus was accompanied by a temporal focusing of the responses characterized by a clear tightening of the latency and narrowing of the peak of activity, which was often accompanied by some level of tonic inhibition of the background discharge. Thus, LC stimulation increased the signal-to-noise ratio of SI neuronal responses to skin stimulation. When inhibitory effects were induced by LC stimulation, they clearly affected the unit response to the first air puff, which was severely depressed. However, the response to the second puff could be facilitated, suggesting that LC stimulation might have produced inhibition of those inhibitory interneurons responsible for the postexcitatory inhibition of the units under examination. Evidence for spatial focusing of the response was not easily documented. In some units, however, LC stimulation produced either facilitation of the responses to puffs at the receptive field center and inhibition of the responses to puffs at the edge at the receptive field or vice versa. 6. Since the LC complex contains in the rat a predominant population of noradrenergic neurons, it is likely that the effects described above were mainly due to activation of these noradrenergic neurons. 7. The effects of LC stimulation on the responses of SI cortical units to natural or electrical skin stimulation had a recovery period of about 4 minutes after the end of stimulation. These findings can be related to the fact that noradrenaline, which is released by LC stimulation, does not act on target neurons as a neurotransmitter, but rather as a neuromodulator, through second messengers. Since LC activity increases during wakefulness, it might contribute through temporal and possibly spatial focusing of the responses to activate molecular mechanisms which, like induction of immediate-early genes, may strengthen both perception and conscious awareness as well as sensorimotor integration
Changes in gain and spatiotemporal properties of the vestibulospinal reflex after injection of a GABAA agonist in the cerebellar anterior vermis.
No full textAbstract
Experiments were performed to study the influence of the cerebellar anterior vermis on both amplitude and directional properties of the vestibulospinal (VS) reflexes. In decerebrate cats, the multiunit EMG activity of the medial head of the forelimb extensor triceps brachii was recorded during wobble of the whole animal at 0.15 Hz. With this procedure the animals were submitted to a tilt characterized by a fixed amplitude (10°) and by a direction moving at constant velocity over the horizontal plane, in both a clockwise (CW) and a counterclockwise (CCW) direction. These dynamic stimuli permitted characterization of the triceps muscle response to animal tilt as a single vector in the horizontal plane. The gain of this vector was taken as the mean value obtained for the CW and CCW responses, while its orientation corresponded to the direction of head displacement, lying midway between the maximal response directions to CW and CCW rotations. The temporal phase was evaluated as the half difference between the directions of the CW and CCW responses. In all the experiments the response vector of the triceps brachii was closely aligned with the transverse axis and pointed to the side-down direction. Unilateral inactivation of the cerebellar anterior vermis after microinjection, in one or two folia of lobule V, of the GABA-A agonist muscimol (0.5 μL at 8 μg/μL saline), consistently and reversibly reduced in 20 to 40 min the amplitude of the EMG modulation of the ipsilateral triceps brachii to 46% to 80% of the control value, while only a small shift (up to 30°) of the response vector occurred either nosewards or tailwards. Small shifts in temporal phase were also observed. These findings suggest that the Purkinje (P)-cells, which usually fire out of phase with respect to the VS neurons, contribute positively to the amplitude of the VS reflexes. It was previously shown that P-cells with response vectors covering all the directions of animal displacement are present in small regions of the cerebellar anterior vermis; it is likely that these neurons represent functional units facilitating the VS reflexes elicited by animal tilt in the direction of their response vectors. By suppressing the activity of these cells, muscimol injections would lead to a general depression of the triceps responses to animal displacement, not associated with prominent changes in directional specificity
Microinjections of GABAergic agents in the locus coeruleus modify the gain of vestibulospinal reflexes in decerebrate cats.
No full textAbstract
1. Precollicular decerebrate cats show a good postural activity in the four limbs and a small-amplitude vestibulospinal (VS) reflex, as revealed by recording the EMG response of the triceps brachii to sinusoidal roll tilt of the animal at 0.15 Hz, +/- 10 degrees. This preparation was used to study whether inactivation of the locus coeruleus (LC) elicited by local administration either of the GABA-A agonist muscimol or of the GABA-B baclofen produced changes in posture as well as in gain of the VS reflexes. 2. Microinjection into the LC of one side of 0.13-0.25 microliter of a muscimol or baclofen solution (at 2.5 or 1 microgram/microliter saline, respectively) stained with 5% pontamine, usually decreased the extensor tonus in the ipsilateral limbs and to a lesser extent also in the contralateral limbs. However, the amplitude of modulation and thus the gain of the first harmonic component of the multiunit EMG responses of the ipsilateral and to a lesser extent also of the contralateral triceps brachii to the same parameters of labyrinth stimulation increased. The phase angle of the responses remained nearly unchanged by this treatment. The effects appeared 5-10 min after the injection of muscimol, fully developed in 30 min and progressively declined within the following 2-2.5 hours. 3. The increased gain of the VS reflexes acting on the triceps brachii did not depend on the decreased postural activity following the injection of the GABA-A or GABA-B agonist, since it was still observed if the reduced EMG activity following the injection was compensated by an increased static stretch of the muscle. Moreover, the postural and reflex changes described above were not due to irritative events following the injection, since they were not observed in control experiments following injection of 0.25 microliter saline within the LC-complex. On the other hand, postural and reflex changes opposite in sign to those elicited by muscimol or baclofen were obtained by local injection into the LC-complex of a GABA-A or GABA-B antagonist (0.25 microliter of bicuculline or faclofen at 8 micrograms/microliters saline). 4. In some experiments, the decrease in postural activity of the forelimbs after injection of muscimol into the LC complex was followed by transient episodes of postural atonia, which affected not only the ipsilateral but also the contralateral triceps muscles.(ABSTRACT TRUNCATED AT 400 WORDS
Proprioceptive neck influences modify the information about tilt direction coded by the cerebellar anterior vermis.
No full textAbstract
Objective - To verify whether the direction of head tilt coded by the population response of Purkinje (P) cells located in the cerebellar anterior vermis is modified by the relative position of the body with respect to the head. Material and Methods - In decerebrate cats, the responses of P cells to wobble of the whole animal were analyzed in order to compute the response vectors of the same cells to the labyrinthine input. These response vectors were used to evaluate the population response (vector) of all the recorded neurons to head tilt in specific directions. Results - When the head was aligned with the body, the direction of the population vector closely corresponded to that of head tilt. A 30° body-to-head rotation to the left or right around a C1-C2 vertical axis modified the response vectors of most of the recorded neurons, leading to reciprocal deviations of the population vector from the direction of head tilt of ≈30°. Conclusion - We propose that information from neck receptors regulates the convergence of labyrinthine signals with different spatial and temporal properties on corticocerebellar units, thus allowing the P-cell population to code the direction of body tilt
Coupling sensory inputs to the appropriate motor responses: new aspects of cerebellar function.
No full textAbstract
It is known that proprioceptive signals modify the spatial organization of the postural reflexes, thus leading to body stability. The neurophysiological basis of this phenomenon are at present unknown. The present report documents that, in decerebrate cat, body-to-head rotation in the horizontal plane modified the preferred response direction to labyrinthine stimulation of the forelimb extensor triceps brachii. Such direction resulted always perpendicular to the longitudinal body axis of the animal, whatever its relative position with respect to the head could be. The rotation of the preferred response direction of the triceps was greatly reduced by functional inactivation of the ipsilateral cerebellar vermis. On the other hand, following body-to-head displacement, the preferred response directions of the corresponding P-cells tended, on the average, to rotate in the same direction and by the same angle as the body. We propose that the neck input finely tunes parallel vestibular channels, endowed with different spatial and temporal properties, impinging upon P-cells, thus modifying their responses to animal tilt and, as a consequence, the spatial properties of VS reflexes. It is possible that, by a similar mechanism, the cerebellum may contribute to the changes in reference frame occurring in sensorimotor transformations of reflex and voluntary nature
Neck influences on the spatial properties of vestibulospinal reflexes in decerebrate cats: role of the cerebellar anterior vermis.
No full textAbstract
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°, 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°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
Responses of Purkinje cells in the cerebellar anterior vermis to off-vertical axis rotation in decerebrate cats.
No full textAbstract
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 (OVER). 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 bidirectiol tal units, the direction of maximum sensitivity to tilt (S(max) could be identified. S(max) 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 cosine-tuned 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 S(max) direction and declined with the cosine of the angle between S(max) 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 (undirectional 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
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