Phasic, Nonsynaptic GABA-A Receptor-Mediated Inhibition Entrains Thalamocortical Oscillations

• DOI: 10.1523/jneurosci.4386-13.2014
• Publication Date: 2014-05-21T17:05:00Z
• Authors: Zita Rovó; Ferenc Mátyás; Péter Barthó; Andrea Slézia; Sandro Lecci; Chiara Pellegrini; Simone Astori; Csaba Dávid; Balázs Hangya; Anita Lüthi; László Acsády
• Keywords: Cerebral Cortex; Neurons; 0303 health sciences; Mice, Transgenic; Neural Inhibition; Dependovirus; Receptors, GABA-A; GABA Antagonists; Mice, Inbred C57BL; Pyridazines; Mice; 03 medical and health sciences; Inhibitory Postsynaptic Potentials; Thalamus; Synapses; Vesicular Glutamate Transport Protein 2; Animals; Excitatory Amino Acid Antagonists; gamma-Aminobutyric Acid

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.