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Modulation of Purkinje cell response to glutamate during the sleep-waking cycle.
Abstract
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
Immediate-early gene (IEG) expression during sleep (S) and waking (W) in prolonged continuous illumination (LL)
Hipnic modulation of cerebellar information processing: implications for the cerebro-cerebellar dialogue
Recent 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
Experimental 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
Fos-protein expression in noradrenergic locus coeruleus neurons after unilateral labyrinthectomy in the rat
The locus coeruleus and Fos-protein expression in vestibular compensation
c-Fos mRNA and the related Fos-protein are rapidly induced by physiological stimuli and can be used as molecular markers of neural activation and plasticity, We have recently shown that unilateral labyrinthectomy (UL) produced in rats an asymmetric increase of the c-fos and Fos-protein expression not only in the vestibular nuclei, the inferior olive. the cerebellar cortex and the caudate-putamen. as reported in previous studies. but also in the locus coeruleus (LC)-complex. particularly of the intact side, whose neurons integrate labyrinthine signals and are apparently involved in the plastic changes which are at the basis of vestibular compensation. The putative noradrenergic nature of the Fos-positive LC-complex neurons observed after UL was studied by combining Fos-protein immunocytochemistry with the immunocytochemical detection of tyrosine hydroxylase (TH), one of the synthetizing enzymes of noradrenaline (NA). It was then possible to verify that Fos-positive LC-complex neurons were presumably noradrenergic in nature, as they could be double labeled with the Fos/TH technique. This finding appeared 3h after the lesion. decreased 6 h after UL and disappeared after 24 h, when partial compensation of the vestibular syndrome had occurred, Thus, UL results in asymmetric functional activation in the LC-complex of noradrenergic neurons. This observation was attributed to the fact that asymmetric stimulation of labyrinth receptors gives rise to asymmetric changes in firing rate of LC neurons. Since these neurons send noradrenergic afferents to several target structures such as the vestibular nuclei, the inferior olive, the cerebellar cortex and the caudate-putamen, we postulated that the asymmetric,activation of the noradrenergic LC system after in could increase the Fos-protein expression in the above mentioned target structures. thus representing a key factor in determining the plastic changes, which are at the basis of vestibular compensation
ARRIGHI (P.), GROSJEAN (R.), JEHASSE (L.), TAVIANI (H.), ETTORI (F.) et EMMANUELU (R.), Histoire de la Corse (publiée sous la direction de P. Arrighi)
Ambrosi C. ARRIGHI (P.), GROSJEAN (R.), JEHASSE (L.), TAVIANI (H.), ETTORI (F.) et EMMANUELU (R.), Histoire de la Corse (publiée sous la direction de P. Arrighi). In: Annales. Economies, sociétés, civilisations. 30ᵉ année, N. 4, 1975. pp. 867-868
ARRIGHI (P.), GROSJEAN (R.), JEHASSE (L.), TAVIANI (H.), ETTORI (F.) et EMMANUELU (R.), Histoire de la Corse (publiée sous la direction de P. Arrighi)
Ambrosi C. ARRIGHI (P.), GROSJEAN (R.), JEHASSE (L.), TAVIANI (H.), ETTORI (F.) et EMMANUELU (R.), Histoire de la Corse (publiée sous la direction de P. Arrighi). In: Annales. Economies, sociétés, civilisations. 30ᵉ année, N. 4, 1975. pp. 867-868
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