Medial Parabrachial Nucleus Is Essential in Controlling Wakefulness in Rats

Abstract

Activation of the parabrachial nucleus (PB) in the brainstem induced wakefulness in rats, suggesting which is an important nucleus that controls arousal. However, the sub-regions of PB in regulating sleep-wake cycle is still unclear. Here, we employ chemogenetics and optogenetics strategies and find that activation of the medial part of PB (MPB), but not the lateral part, induces continuous wakefulness for 10 h without sleep rebound in neither sleep amount nor the power spectra. Optogenetic activation of glutamatergic MPB neurons in sleeping rats immediately wake rats mediated by the basal forebrain (BF) and lateral hypothalamus (LH), but not the ventral medial thalamus. Most importantly, chemogenetic inhibition of PB neurons decreases wakefulness for 10 h. Conclusively, these findings indicate that the glutamatergic MPB neurons are essential in controlling wakefulness, and that MPB-BF and MPB-LH pathways are the major neuronal circuits.

Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice

“…[在此处键入] 7 of the solitary tract (NTS) have been demonstrated to be essential in controlling wakefulness [10,27,28] and the PB innervates PVH vglut2 neurons to form bidirectional connections. In addition, the PVH vglut2 -LSv pathway is involved in the regulation of feeding, which is a wakefulness-required behavior [29].…”

“…As shown in Figure 1E and Figure 1—figure supplement 1 , we found that PVH vglut2 neurons received direct inputs from many regions. Among them, the PVT and PB are considered as two important wake-promoting nuclei; they exhibit higher activities during wakefulness than during sleep, and their activation induces rapid transitions from sleep to wakefulness ( Ren et al, 2018 ; Qiu et al, 2016 ; Xu et al, 2021 ). Therefore, we speculated that PVH vglut2 neurons might act as a crucial node for the control of wakefulness.…”

“…We found that PVH vglut2 neurons projected to diverse neuroanatomical sites ( Figure 5—figure supplement 1C , 1 Figure 5—source data 1 ). Among them, the PB, PVT and nucleus of the solitary tract (NTS) have been demonstrated to be essential in controlling wakefulness ( Ren et al, 2018 ; Qiu et al, 2016 ; Xu et al, 2021 ) and the PB innervates PVH vglut2 neurons to form bidirectional connections. In addition, the PVH vglut2 -LSv pathway is involved in the regulation of feeding, which is a wakefulness-required behavior ( Xu et al, 2019 ).…”

Convergence of monosynaptic inputs from neurons in the brainstem and forebrain on parabrachial neurons that project to the paraventricular nucleus of the thalamus

“…It is generally appreciated that arousal and the maintenance of wakefulness are mediated by a highly distributed network of interconnected neurons that span the forebrain, midbrain, and hindbrain (Liu and Dan 2019;Jones 2020;Scammell et al 2017). The PB has been identified as a critical brainstem structure involved in arousal from sleep via connections to the basal forebrain and the LH (Venner et al 2019;Qiu et al 2016;Fuller et al 2011;Xu et al 2021;Kaur et al 2013;Kaur et al 2017). While there is some evidence that the PVT is involved in arousal from sleep (Hua et al 2018;Matyas et al 2018;Ren et al 2018), other evidence indicates that the thalamus is not critical for the PB's cortical arousal effects (Qiu et al 2016;Fuller et al 2011.…”

Whole Brain Mapping of Neurons Innervating Extraorbital Lacrimal Glands in Mice and Rats of Both Genders

“…The PB can be divided along the superior cerebellar peduncle into three main parts: PBI, PBmm, and PBKF, all of which showed a substantial quantity of labeled neurons from our results (Fulwiler and Saper, 1984). Several pioneer studies have outlined that the PBI is vital in transmitting a broad range of sensory information such as feeding and pain to the forebrain (Le May et al, 2021), the PBKF is mainly involved in breathing rhythmogenesis (Yang et al, 2020), and the PBmm plays an important role in controlling wakefulness and behavioral arousal (Xu et al, 2021). All the functional capacities of PB subregions mentioned above and their heavy innervation to ELGs may facilitate the formation of associations between external stimuli and behavior outcomes, which also underlies the sin qua non role of ELGs in social behaviors.…”