title: [Wakefulness and central basal nuclei: experimental observations and possible implications in Parkinson's disease].
abstract: Movement disorders in Parkinson disease, notably dampened during sleep, are associated with hyperactivity of the subthalamic nucleus (STN), whose origin is controversial. We have studied, on non-anaesthetized head-restrained rats, the STN spontaneous unit activity and the one of its principal GABAergic afferents, the globus pallidus (GP). In normal rats, STN neurons shifted from a random discharge in wakefulness (W) to a bursting pattern in slow wave sleep (SWS), without any change in their mean firing rate. In contrast GP neurons, with a mean firing rate higher in W than in SWS, exhibited a relatively regular discharge rate whatever the vigilance state. During paradoxical sleep, both STN and GP neurons increased markedly their firing rate. When applied during W, GABA-A antagonists increased the STN firing rate but did not change the typical W random pattern. When applied during SWS, they strongly reinforced the spontaneous burst pattern into a particularly marked one with instantaneous frequencies reaching 500Hz. SWS-W transitions occurring during ongoing antagonist iontophoresis invariably disrupted this burst pattern into a random one. On 6-OHDA unilaterally treated rats, the ipsilateral STN was hyperactive whatever the vigilance state (with an abnormal burst pattern during W on some neurons), but this hyperactivity did not seem to be associated with a GP hypoactivity. These results show that STN activity is not inversely correlated with GP activity, that its discharge pattern is strongly dependent on vigilance states, that GABA receptors do not play an exclusive role in regulating its firing pattern, and question the depolarization block hypothesis during STN high frequency stimulation.
authors.affiliation: Laboratoire de Neuropharmacologie, INSERM U512, Université Claude Bernard Lyon1, 8, avenue Rockefeller, 69373 Lyon.
authors.forename: G
authors.initials: G
authors.lastname: Chouvet
authors.forename: N
authors.initials: N
authors.lastname: Urbain
authors.forename: N
authors.initials: N
authors.lastname: Vautrelle
authors.forename: L
authors.initials: L
authors.lastname: Dahan
authors.forename: B
authors.initials: B
authors.lastname: Astier
authors.forename: B
authors.initials: B
authors.lastname: Renaud
mesh_terms: D000818:Animals; D006801:Humans; D007478:Iontophoresis; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000503:physiopathology*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology; D051381:Rats; D012894:Sleep Stages / Q000502:physiology*; D012893:Sleep Wake Disorders / Q000139:chemically induced / Q000503:physiopathology; D020531:Subthalamic Nucleus / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents; D016627:Oxidopamine