The midbrain reticular formation (MRF) and periaqueductal gray (PAG) are two adjacent brain regions associated with regulating defensive behaviours, nociception and sleep. They comprise mainly inhibitory GABAergic and excitatory glutamatergic neurons; however, the molecular profiles and differential functions of GABAergic neuron sub-types in these regions remain largely elusive. Juha Partanen, Kaia Achim and colleagues have previously demonstrated that the transcription factor Gata2 is required for the development of all embryonic midbrain-derived GABAergic neurons. In this latest study, they elaborate on these findings, showing that Gata2 is required for expression of the transcription factor Nkx2-2 and that both, in turn, are required for expression of the transcriptional repressor Skor2. Based on differences in electrophysiological properties and neuronal morphology, the authors suggest subtypes of Skor2-expressing neurons likely also exist. Specifically, Nkx2-2 and Skor2 co-expressing GABAergic neurons, found at the boundary of the dorsal MRF and ventral PAG, are activated by rapid eye movement (REM) sleep deprivation and project to the dorsolateral pons, which controls REM sleep. These characteristics match those of REM-off neurons found in the midbrain, and thus suggest that this group of GABAergic neurons, defined by Gata2, Nkx2-2 and Skor2 expression, is involved in sleep regulation. These findings therefore enhance our understanding of the drivers and molecular distinctions of midbrain GABAergic neurons.
