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Authors & Affiliations
Wei-Chen Hung, Hsiu-Wen Yang, Ming-Yuan Min
Abstract
Noradrenergic (NA) neurons originating from the locus coeruleus (LC) serve as the primary source of noradrenaline in the brain and play a critical role in arousal and cognitive functions. Previous studies have shown a potential link between astrocyte activity in the LC and emotional dysfunction, and suggested that astrocytes may influence NA neuron activity by modulating extracellular ion and neurotransmitter concentrations or by releasing gliotransmitters. However, there is currently no evidence for direct communication between astrocytes and NA neurons in the LC. In this study, we addressed this question by investigating the effect of selective optogenetic activation of astrocytes expressing Aldh1l1 on the responses of LC-NA neurons. We found that photo-stimulation of Aldh1l1 astrocytes induced a large inward current in NA neurons as well as a significant increase in spontaneous EPSC activity. These effects were caused by the release of glutamate from the astrocytes, which activated mainly at AMPA and NMDA receptors. Furthermore, there was an increase in the frequency of slow inward currents (SIC) and the incidence of spontaneous phasic activity both during opto-stimulation and in the following 20 minutes. Consistent with the notion that SICs are mediated by astrocytic release of glutamate acting on extrasynaptic NMDA receptors, we found that application of NMDA receptor antagonists, specifically DL-AP5, successfully attenuated SIC activity. In conclusion, the present results provide, for the first time, evidence for indirect modulation of excitability and synaptic activity of LC NA neurons by Aldh1l1 astrocytes through glutamatergic transmission