Slow intrinsic oscillations in the ventrolateral preoptic nucleus

Abstract The ventrolateral preoptic nucleus (VLPO) of the hypothalamus plays a major role in the induction and consolidation of non-rapid eye movement (NREM) sleep. While VLPO neurons are heterogeneous, they often display low-threshold spikes (LTS), a feature that supports rhythmic activity. Nevertheless, rhythmic bursting in these VLPO neurons has never been observed. Here, we report that ∼12% of VLPO neurons in a large database of ex vivo patch-clamp recordings display spontaneous rhythmic bursting of action potentials. This activity occurred in putative sleep-promoting neurons, identified by inhibitory responses to noradrenaline (NA), as well as wake-active neurons that were activated by NA. Unsupervised clustering of 24 neurons based on burst properties, electrophysiological, and morphological features revealed three distinct groups: one corresponding to putative sleep-promoting neurons and two wake-active neurons with fast and slow bursting dynamics. Strikingly, membrane potential oscillations persisted in the presence of tetrodotoxin (TTX), indicating that rhythmic bursting is driven by intrinsic mechanisms rather than network activity. These findings suggest that rhythmic bursting is an intrinsic and functionally relevant mode of activity in VLPO neurons, which may contribute to sleep regulation.