Increase in NREM sleep slow waves following injections of sodium oxybate in the mouse cerebral cortex and the role of somatostatin‐positive interneurons

• Published in: The European journal of neuroscience 2024-02, Vol.59 (4), p.502-525
• Main Authors: Spano, Giovanna Maria, Cavelli, Matias, Marshall, William, Tononi, Giulio, Cirelli, Chiara
• Format: Article
• Language: English
• Subjects: Cerebral cortex; chemogenetic; Cortex (frontal); Cortex (motor); Cortex (parietal); GABAb; Injection; Interneurons; mouse; NREM sleep; REM sleep; Sleep; Sodium; Somatostatin; γ-Aminobutyric acid B receptors
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.15846

The systemic administration of sodium oxybate (SXB), the sodium salt of gamma‐hydroxybutyric acid, promotes slow wave activity (SWA, 0.5–4 Hz EEG power) and increases non‐rapid eye movement (NREM) sleep. These effects are mediated by the widely expressed GABAb receptors, and thus, the brain areas targeted by SXB remain unclear. Because slow waves are mainly a cortical phenomenon, we tested here whether systemic SXB promotes SWA by acting directly on the cortex. Moreover, because somatostatin (SOM) + cortical interneurons play a key role in SWA generation, we also assessed their contribution to the effects of SXB. In adult SOM‐Cre mice, the injection of SXB in left secondary motor cortex increased SWA during NREM sleep in the first 30 min post‐injection (11 mice: either sex). SWA, the amplitude and frequency of the slow waves, and the frequency of the OFF periods increased ipsilaterally and contralaterally to the SXB injection in frontal and parietal cortex. All these changes disappeared when the intracortical injection of SXB was preceded by the chemogenetic inhibition of the SOM+ cells. Thus, SXB may promote the slow waves of NREM sleep, at least in part, by acting directly on the cortex, and this effect involves GABAergic SOM+ interneurons. Our working hypothesis is that SXB potentiates the ability of these cells to inhibit all other cortical cell types via a GABAb mechanism, thus promoting the transition from ON to OFF periods during NREM sleep. When given systemically, sodium oxybate (SXB) is known to promote slow wave activity (SWA) and increase non‐rapid eye movement (NREM) sleep through a GABAb mechanism, but the brain regions mediating these effects remain elusive. This study shows that SXB injected locally in the cerebral cortex can promote the slow waves of NREM sleep and that the somatostatin (SOM) + cortical interneurons are involved in this effect.