title: 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.
authors.affiliation: Dipartimento di Fisiologia e Biochimica, Universita' di Pisa, Via S. Zeno 31, I-56127, Pisa, Italy. anp@dfb.unipi.it
authors.forename: P
authors.initials: P
authors.lastname: Andre
authors.forename: P
authors.initials: P
authors.lastname: Arrighi
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004569:Electroencephalography / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology*; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
chemical_list: D018698:Glutamic Acid