Lateral hypothalamic astrocytes contribute to the hypercapnic chemoreflex in a light-dark cycle-dependent manner in unanesthetized rats

Brainstem astrocytes are important for CO2/H+ chemoreception. Lateral Hypothalamus/Perifornicial Area (LH/PFA) neurons have an excitatory effect on the ventilatory response to CO2, however the role of the astrocytes is unknown. We hypothesized that LH/PFA astrocytes play an excitatory role in the hypercapnic ventilatory response in a sleep-wake and light-dark cycles-dependent manner. We manipulated the activity of astrocytes in the LH/PFA of male Wistar rats through microinjection of Fluorocitrate (Fct), which selectively affects astrocytes, inducing the exocytosis of gliotransmitters. We investigated the effects of intra-LH/PFA Fct microinjection on resting breathing and ventilatory responses to hypercapnia and hypoxia during wakefulness and NREM sleep, in the light and dark phases. Fct increased ventilation during hypercapnia but not during room air or hypoxia. The hypercapnic chemoreflex was increased exclusively during the dark-active phase during both, wakefulness and NREM sleep, indicating that LH/PFA astrocytes play an excitatory role in hypercapnic ventilatory response in a light-dark cycle-dependent manner.