Hypoxia sensitive neurons in the caudal hypothalamus project to the periaqueductal gray

Previous studies have demonstrated that the caudal hypothalamus modulates the respiratory responses to hypoxia and hypercapnia. In addition, many of the neurons in this area have a basal discharge related to the cardiac and/or respiratory cycles and are stimulated by hypoxia or hypercapnia. The purpose of the present study was to determine if these hypothalamic neurons project to a known cardiorespiratory area, the periaqueductal gray in the rat. In a first set of experiments, rhodamine-tagged microspheres were injected into the periaqueductal gray (PAG) to determine the areas of the caudal hypothalamus that project to the PAG. These studies revealed that the caudal hypothalamus sends strong ipsilateral and weak contralateral projections to the PAG. In a second set of experiments, single unit recordings were made from neurons in the caudal hypothalamus; the basal discharge of these neurons were examined with signal averaging techniques. Each neuron (n = 79) was tested for a response to inhalation of a hypoxic (10% O2) and a hypercapnic (5% CO2) gas. Antidromic activation techniques were then used to determine if neurons in the caudal hypothalamus send projections to or through the PAG. Nineteen percent (n = 15) of the hypothalamic neurons studied could be activated from the PAG; approximately 53% (n = 8) of these were excited by hypoxia and 27% (n = 4) by hypercapnia. Most of these neurons tested (42 of 64 neurons) had a basal discharge related temporally to the cardiac and/or respiratory cycles. These findings suggest that a caudal hypothalamic to periaqueductal gray projection is involved in the integrated response to hypoxia.