GABA(B) and NMDA receptors contribute to spindle-like oscillations in rat thalamus in vitro.
Thalamic slice preparations, in which intrathalamic connectivity between the reticular nucleus and relay nuclei is maintained, are capable of sustaining rhythmic burst firing activity in rodents and ferret. These in vitro oscillations occur spontaneously in the ferret and have frequencies (6-10 Hz) within the range of sleep spindles observed in vivo. In the rat, mainly lower frequency (2-4 Hz) oscillations, evoked under conditions of low bath [Mg(2+)] and/or GABA(A) receptor blockade, have been described. Here we show that faster rhythms in the range of 4-9 Hz can be evoked in rat thalamic slices by electrical stimulation of the internal capsule and also occur spontaneously. When bath [Mg(2+)] was 2 mM, these spindle-like oscillations were most common in a brief developmental time window, peaking at postnatal day 12 (P12). The oscillations were almost completely blocked by the GABA(A) receptor antagonist picrotoxin, and, in some cases, the frequency of oscillations was increased by the GABA(B) receptor antagonist CGP-35348. The selective blockade of N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by the antagonists 2-amino-5-phosphonovaleric acid or 1,2,3,4-Tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), respectively, significantly shortened oscillations but did not completely block them. A combination of the two drugs was necessary to abolish oscillatory activity. The barbituate pentobarbital, which enhances GABA(A)R responses, initially slowed and synchronized oscillations before completely blocking them. When bath [Mg(2+)] was reduced from 2 to 0.65 mM, evoked oscillations became more robust and were often accompanied by spontaneously arising oscillations. Under these conditions, GABA(A) receptor blockade no longer inhibited oscillations, but instead converted them into the slow, synchronous rhythms that have been observed in other studies. The effects of GABA(B) or NMDA receptor blockade were more pronounced in 0.65 mM than in 2 mM external [Mg(2+)]. Thus spindle-like oscillations occur in rat thalamic slices in vitro, and we find that, in addition to the previously demonstrated contributions of GABA(A) and AMPA receptors to these oscillations, NMDA and GABA(B) receptors are also involved. The strong influence of external [Mg(2+)] on GABAergic pharmacology and a contribution of NMDA receptors during oscillations suggest a link between the excitability of NMDA receptors and the activation of GABA(B)R-mediated inhibitory postsynaptic currents.
Jacobsen
R B
RB
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ulrich
D
D
Huguenard
J R
JR
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005583:Fourier Analysis; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010507:Periodicity; D010852:Picrotoxin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013045:Species Specificity; D013788:Thalamus / Q000502:physiology*
D015763:2-Amino-5-phosphonovalerate; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018757:GABA Modulators; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D008274:Magnesium; D009943:Organophosphorus Compounds; D010424:Pentobarbital; D010852:Picrotoxin; D011810:Quinoxalines; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C066430:CGP 35348