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Sleep is an autonomous process and is not always under our direct and voluntary control. Awake or asleep, we are basically under the regulation of two biological processes: sleep homeostasis, commonly known as 'sleep pressure', and circadian rhythm, otherwise known as 'the biological clock'. These two processes work in harmony to promote a good sleep consolidated at night.
The ventrolateral preoptic nucleus (VLPO) in the brain plays a critical role in falling – and staying – asleep, while the posterior lateral portion of the hypothalamus contains neurons (brain cells) that play a role in the maintenance of staying awake, including orexin neurons in the lateral hypothalamic zone (LHA) and histaminergic neurons in the tuberomammillary nucleus (MNT). To date, however, the precise connectivities between these cell populations remain unclear.
"In our study, we aimed to identify the key players involved in awake regulation," says Yuki Saito, who headed a Tsukuba university. "To achieve the goal of the study, we focused on hypothalamic neuron populations, histaminergic histamine-positive histidine decarboxylase (HDC +) neurons (HDC neurons) in the GTA and the team. used recombinant rabies virus-mediated trans-synaptic tracing in the mouse brain to badyze the architecture and function of the hypothalamic circuits that link the neuronal populations involved in sleep / wake regulation. discovered that these neurons linked to the excitation are strongly innervated by GABAergic neurons in the preoptic zone, including VLPO.
The team then characterized GABAergic neurons in VLPOs (GABAVLPO neurons) which established direct synaptic contact with the hypothalamic neurons These two groups of neurons overlapped and were both strongly inhibited by naline and serotonin, showing typical electrophysiological features of sleep promoter neurons in VLPO
"Taken together, our findings provide direct evidence of monosynaptic connectivity between GABAVLPO neurons and hypothalamic excitation neurons and identify the effects monoamines on these neuronal pathways, "says Takeshi Sakurai, corresponding author of the study. "This information is important for us to better understand the mechanisms that control sleep and wakefulness, which can lead to the development of reliable recommendations for restful sleep."
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