We have recently identified a distinct subtype of sleep-promoting GABAergic neurons in the dorsolateral hypothalamus that express the transcription factor Lhx6 (termed Lhx6 neurons)(Liu et al., 2017. Nature). Lhx6 neurons are activated in response to sleep-pressure, regulate both REM and NREM sleep and able to self-inhibit each other. In addition, Lhx6 neurons form pre- and post-synaptic connections with multiple wake-active and REM-inhibiting neurons in midbrain regions, and Lhx6 neurons are able to inhibit wake-promoting orexigenic neurons of the lateral hypothalamus.

These sleep-promoting Lhx6 neurons are also molecularly heterogeneous and show extensive diversity in transcription factor expression during development. Using scRNA-Seq and conditional knockout lines, we aim to identify gene regulatory networks that specify distinct subtypes of Lhx6 neurons during development.

Representative images of Fos immunostaining (red) and Lhx6–eGFP expression (green) in ventral zona incerta (VZI)

Liu K, Kim J, Kim DW, Zhang S, Denaxa M, Bao H, Lim SA, Kim E, Liu C, Wickersham IR, Pachinis V, Hattar S, Song J, Brown SR, and Blackshaw S. Lhx6-positive GABAergic neurons of the zona incerta promote sleep.  Nature 2017 548:582-587

https://doi.org/10.1038/nature23663