Glutamatergic-receptors blockade does not regularize the slow wave sleep bursty pattern of subthalamic neurons.
The subthalamic nucleus (STN) has been implicated in movement disorders observed in Parkinson's disease because of its pathological mixed burst firing mode and hyperactivity. In physiological conditions, STN bursty pattern has been shown to be dependent on slow wave cortical activity. Indeed, cortical ablation abolished STN bursting activity in urethane-anaesthetized intact or dopamine depleted rats. Thus, glutamate afferents might be involved in STN bursting activity during slow wave sleep (SWS) when thalamic and cortical cells oscillate in a low-frequency range. The present work was aimed to test, on non-anaesthetized rats, if it was possible to regularize the SWS STN bursty pattern by microiontophoresis of kynurenate, a broad-spectrum glutamate ionotropic receptors antagonist. As glutamatergic effects might be masked by GABAergic inputs arriving tonically and during the entire sleep-wake cycle on STN neurons, kynurenate was also co-iontophoresed with bicuculline, a GABA(A) receptors antagonist. Kynurenate iontophoretic applications had a weak inhibitory effect on the discharge rate of STN neurons whatever the vigilance state, and did not regularize the SWS STN bursty pattern. But, the robust bursty bicuculline-induced pattern was impaired by kynurenate, which elicited the emergence of single spikes between remaining bursts. These data indicate that the bursty pattern exhibited by STN neurons specifically in SWS, does not seem to exclusively depend on glutamatergic inputs to STN cells. Furthermore, GABA(A) receptors may play a critical role in regulating the influence of excitatory inputs on STN cells.
Urbain
Nadia
N
Neurobiological Psychiatry Unit, McGill University, 1033 avenue des Pins Ouest, Montreal, Quebec, H3A 1A1, Canada. nadia.urbain@laposte.net
Vautrelle
Nicolas
N
Dahan
Lionel
L
Savasta
Marc
M
Chouvet
Guy
G
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D007478:Iontophoresis / Q000379:methods; D007736:Kynurenic Acid / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D020531:Subthalamic Nucleus / Q000166:cytology*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018698:Glutamic Acid; D007736:Kynurenic Acid; D001640:Bicuculline