The research team led by Prof. Shumin Duan and Yan-qin Yu has recently published a study in Advanced Science titled Adenosine‐Dependent Arousal Induced by Astrocytes in a Brainstem Circuit on October 16, 2024 This study provides the first evidence that astrocytes in the brainstem parafacial zone (PZ) play a unique role in promoting and sustaining wakefulness through extracellular adenosine and elucidates the underlying circuit-level mechanisms.

Astrocytes play a crucial role in regulating sleep-wake behavior. However, how astrocytes govern a specific sleep-arousal circuit remains unknown. Here, the authors show that parafacial zone (PZ) astrocytes responded to sleep-wake cycles with state-differential Ca²⁺ activity, peaking during transitions from sleep to wakefulness. Using chemogenetic and optogenetic approaches, they found that activating PZ astrocytes elicited and sustained wakefulness by prolonging arousal episodes, while impeding transitions from wakefulness to non-rapid eye movement (NREM) sleep. Activation of PZ astrocytes specially induced the elevation of extracellular adenosine through the ATP hydrolysis pathway but not equilibrative nucleoside transporter (ENT) mediated transportation. Strikingly, the rise in adenosine levels induced arousal by activating A₁ receptors, suggesting a distinct role for adenosine in the PZ beyond its conventional sleep homeostasis modulation observed in the basal forebrain and cortex. Moreover, at the circuit level, PZ astrocyte activation induced arousal by suppressing the GABA release from the PZ^GABA neurons, which promote NREM sleep and project to the parabrachial nucleus (PB). Thus, their study unveils a distinctive arousal-promoting effect of astrocytes within the PZ through extracellular adenosine, and elucidates the underlying mechanism at the neural circuit level.

Summary of the molecular and neural circuit mechanisms underlying PZ astrocyte activation in sleep-wake regulation.

Website: https://onlinelibrary.wiley.com/doi/10.1002/advs.202407706

SHUMIN DUAN AND YAN-QIN YU'S RESEARCH GROUP: Shumin Duan and Yan-qin Yu's group is dedicated to studying the roles of glial cells in synaptic plasticity and the mechanisms of neuron-glia interactions in health and disease. They use cutting-edge techniques including imaging, fiber photometry, electrophysiology (both in vitro and in vivo), molecular genetics, and optogenetics to conduct deep analysis of higher brain functions such as sensory processing, sleep-wake modulation, and emotion-related diseases such as anxiety and depression, learning and memory.