Phasic, nonsynaptic GABA-A receptor-mediated inhibition entrains thalamocortical oscillations.
GABA-A receptors (GABA-ARs) are typically expressed at synaptic or nonsynaptic sites mediating phasic and tonic inhibition, respectively. These two forms of inhibition conjointly control various network oscillations. To disentangle their roles in thalamocortical rhythms, we focally deleted synaptic, γ2 subunit-containing GABA-ARs in the thalamus using viral intervention in mice. After successful removal of γ2 subunit clusters, spontaneous and evoked GABAergic synaptic currents disappeared in thalamocortical cells when the presynaptic, reticular thalamic (nRT) neurons fired in tonic mode. However, when nRT cells fired in burst mode, slow phasic GABA-AR-mediated events persisted, indicating a dynamic, burst-specific recruitment of nonsynaptic GABA-ARs. In vivo, removal of synaptic GABA-ARs reduced the firing of individual thalamocortical cells but did not abolish slow oscillations or sleep spindles. We conclude that nonsynaptic GABA-ARs are recruited in a phasic manner specifically during burst firing of nRT cells and provide sufficient GABA-AR activation to control major thalamocortical oscillations.
Laboratory of Thalamus Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary, Department of Fundamental Neurosciences, University of Lausanne, Lausanne CH-1005, Switzerland.
Zita
Z
Rovó
Laboratory of Thalamus Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary.
Ferenc
F
Mátyás
Laboratory of Thalamus Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary.
Péter
P
Barthó
Laboratory of Thalamus Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary.
Andrea
A
Slézia
Department of Fundamental Neurosciences, University of Lausanne, Lausanne CH-1005, Switzerland.
Sandro
S
Lecci
Department of Fundamental Neurosciences, University of Lausanne, Lausanne CH-1005, Switzerland.
Chiara
C
Pellegrini
Department of Fundamental Neurosciences, University of Lausanne, Lausanne CH-1005, Switzerland.
Simone
S
Astori
Laboratory of Thalamus Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary.
Csaba
C
Dávid
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary.
Balázs
B
Hangya
Department of Fundamental Neurosciences, University of Lausanne, Lausanne CH-1005, Switzerland, acsady@koki.hu anita.luthi@unil.ch.
Anita
A
Lüthi
Laboratory of Thalamus Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary, acsady@koki.hu anita.luthi@unil.ch.
László
L
Acsády
D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D000229:Dependovirus / Q000235:genetics; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011724:Pyridazines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000235:genetics; D013788:Thalamus / Q000502:physiology*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D011724:Pyridazines; D011963:Receptors, GABA-A; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D005680:gamma-Aminobutyric Acid; C049853:gabazine