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Article Dans Une Revue SLEEP Année : 2023

The role of the hypothalamic Lhx6 GABAergic neurons in REM sleep control

Résumé

A large body of data showed that although the brainstem is necessary and sufficient to generate REM sleep, the lateral hypothalamic area (LHA) and the ventral zona incerta (vZI) contain GABAergic and MCH neurons controlling the state by descending projections [1, 2]. Indeed, a very large number of cFos-positive cells was observed in these regions after REM sleep rebound in rats [3]. Around 75% of these cFos-labeled cells express GAD67 mRNA and are likely GABAergic [2]. Interestingly, it was then shown that 45% of the GABAergic neurons located in the mouse vZI express the LIM homeodomain factor (Lhx6) and are distinct from the REM-active MCH and the wake–active hypocretin-orexin neurons [4]. It has also been shown that Lhx6 vZI neurons increased cFos expression at lights on compared to lights off [4]. We then more specifically showed that around 10% of the Lhx6 neurons in vZI are activated during REM sleep rebound occurring after deprivation in mice and that these neurons constitute one-third of the cFos + neurons localized in the vZI [5]. Only 2% of the Lhx6 neurons in vZI were activated during wake. Altogether, these results suggested that Lxh6 neurons in vZI could be involved in REM sleep but a direct demonstration was needed. In their paper published in this issue, Vidal-Ortiz et al. [6] filled this gap by confirming using calcium imaging that most Lhx6 neurons are active during REM sleep and by demonstrating using optogenetics that they indeed play a role in REM sleep control. In the first part of their study, Vidal-Ortiz et al. [6] recorded specifically the activity of Lhx6 neurons in vZI using calcium imaging in Lhx6-cre mice. They found that 45.5% of the neurons recorded were maximally active during REM sleep and started firing 15 seconds before its onset. Around 30% were maximally active during wake, 11% during wake and REM sleep, and 9% during NREM sleep. Interestingly, the NREM neurons were also activated 15 seconds before sleep onset. These results fit with the previous finding that a large proportion of GABAergic (vesicular GABAergic transporter, vGAT positive) neurons in ZI and LHA discharge maximally during REM sleep [7, 8]. Furthermore, in agreement with the present data, these neurons anticipate REM sleep onset indicating that they could play a role in triggering the state.
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Dates et versions

hal-04441941 , version 1 (13-02-2024)

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Amarine Chancel, Patrice Fort, Pierre-Hervé Luppi. The role of the hypothalamic Lhx6 GABAergic neurons in REM sleep control. SLEEP, 2023, pp.zsad331. ⟨10.1093/sleep/zsad331⟩. ⟨hal-04441941⟩
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