Sleep pressure is differentially regulated by molecularly distinct subtypes of Lhx6-positive and Lhx6-negative neurons of the zona incerta.

ABSTRACT: Sleep pressure, the accumulating drive towards sleep during wakefulness, is shaped by Lhx6-positive GABAergic neurons in the zona incerta (ZI). Here, we show that these neurons are broadly activated both by spontaneous and experimentally-elevated sleep pressure, and remain active for hours into recovery sleep. Activation is stronger in anterior ZI and varies across molecularly defined subgroups: Nkx2-2-positive neurons respond vigorously, whereas Calb2-positive neurons respond weakly. We also identify Lhx6-negative/Slc32a1-positive GABAergic ZI neurons with distinct sleep pressure responses. Selective genetic ablation of Nkx2-2 in Lhx6-positive neurons reduces the number of Lhx6-positive neurons, alters their distribution, blunts sleep pressure-induced activation of both Lhx6-positi

SUBMITTER: Chandler PW 

PROVIDER: S-EPMC12324396 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature