The involvement of microglia in the locus coeruleus (LC) in the sleep-wake cycle and in the respiratory and behavioral response to panicogenic stimuli

Abstract

Noradrenergic neurons located in the locus coeruleus (LC) play a crucial role in respiratory control, stress response and regulation of the sleep-wake cycle. This region is recognized as one of the main centers involved in the promotion of vigil. In addition, studies have shown greater activation of this nucleus in animals that have experienced adversities in early life, such as neonatal separation. These events can predispose individuals to psychiatric disorders, including panic disorder (PD), and hypersensitivity to carbon dioxide (CO2) has been identified as a marker of this disorder, especially in females. Recently, it has been demonstrated that microglial pro-inflammatory responses may constitute a unique chemosensory system for detecting homeostatic threats such as CO2 inhalation (Volmer et al., 2016). Microglia are also capable of directly influencing sleep duration and intensity, and wakefulness-specific patterns of neuronal activity may affect microglial characteristics in brain areas. Few studies have investigated the role of neuroimmune signaling in mediating CO2 responsiveness, but we know that increased CO2 concentrations can trigger defensive responses, and evidence suggests that women have a greater susceptibility to these stress-related disorders.In this study, we intend to investigate the role of LC microglia in the regulation of the sleep/wake cycle, in the ventilatory and behavioral response to CO2 and in the ACR model (repeated cross-adoption).