QPLOT Neurons—Converging on a Thermoregulatory Preoptic Neuronal Population

Abstract

The preoptic area of the hypothalamus is a homeostatic control center. The heterogeneous neurons in this nucleus function to regulate the sleep/wake cycle, reproduction, thirst and hydration, as well as thermogenesis and other metabolic responses. Several recent studies have analyzed preoptic neuronal populations and demonstrated neuronal subtype-specific roles in suppression of thermogenesis. These studies showed similar thermogenesis responses to chemogenetic modulation, and similar synaptic tracing patterns for neurons that were responsive to cold, to inflammatory stimuli, and to violet light. A reanalysis of single-cell/nucleus RNA-sequencing datasets of the preoptic nucleus indicate that these studies have converged on a common neuronal population that when activated, are sufficient to suppress thermogenesis. Expanding on a previous name for these neurons (Q neurons, which reflect their ability to promote quiescence and expression of Qrfp), we propose a new name: QPLOT neurons, to reflect numerous molecular markers of this population and to capture its broader roles in metabolic regulation. Here, we summarize previous findings on this population and present a unified description of QPLOT neurons, the excitatory preoptic neuronal population that integrate a variety of thermal, metabolic, hormonal and environmental stimuli in order to regulate metabolism and thermogenesis.

Prostaglandin EP3 receptor-expressing preoptic neurons bidirectionally control body temperature via tonic GABAergic signaling

“…The DMH contains sympathoexcitatory neurons that innervate the rMR to drive cold-defensive, febrile and stress responses (Zaretskaia et al, 2003;Madden and Morrison, 2004;Nakamura et al, 2005;Nakamura and Morrison, 2011;Kataoka et al, 2014Kataoka et al, , 2020, and we found that cell bodies of rMR-projecting DMH neurons were more often in close contact with GABAergic axons of POA EP3R neurons than glutamatergic axons. Our Our observation that EP3Rs are expressed by both VGLUT2 mRNA-expressing and GAD67 mRNA-expressing POA neuronal groups is consistent with the recent single cell/nucleus RNA sequencing data showing Ptger3 mRNA expression in "excitatory" and "inhibitory" POA cell clusters (Moffitt et al, 2018;Upton et al, 2021).…”

“…Our observation that EP3Rs are expressed by both VGLUT2 mRNA-expressing and GAD67 mRNA-expressing POA neuronal groups is consistent with the recent single cell/nucleus RNA sequencing data showing Ptger3 mRNA expression in “excitatory” and “inhibitory” POA cell clusters (Moffitt et al, 2018; Upton et al, 2021). The abundant GABAergic terminals of POA EP3R →DMH axons might be provided exclusively by the GAD67 mRNA-expressing population.…”

Prostaglandin EP3 receptor–expressing preoptic neurons bidirectionally control body temperature via tonic GABAergic signaling

“…Our observation that EP3Rs are expressed by both VGLUT2 mRNA–expressing and GAD67 mRNA–expressing POA neuronal groups is consistent with the recent single-cell/nucleus RNA sequencing data showing Ptger3 mRNA expression in both “excitatory” and “inhibitory” POA cell clusters ( 52 , 53 ). The abundant GABAergic axons of POA EP3R → DMH neurons might be provided exclusively by the GAD67 mRNA–expressing population.…”

Retinal patterns and the cellular repertoire of neuropsin (Opn5) retinal ganglion cells

“…Furthermore, we identified a set of tdTomato‐labeled fibers overlying optic tract RGC axons, and these appear to project to the supraoptic nucleus (SON, Figure 3a). While RGCs have been shown to innervate the peri‐SON (Beier et al., 2021; Hattar et al., 2006), Opn5 is also expressed in hypothalamic QPLOT neurons that are presynaptic to the SON, and these processes may reflect dendritic or axonal innervation by central QPLOT hypothalamic neurons (Upton et al., 2021; K. X. Zhang et al., 2020).…”