Topographical specificity of regulation of respiratory and renal sympathetic activity by the midbrain dorsolateral periaqueductal gray

Abstract

The midbrain periaqueductal gray (PAG) mediates the physiological responses to a wide range of stressors. It consists of four longitudinal columns that have different anatomical connections and functional properties. Previous anatomical and behavioral studies have led to the hypothesis that the dorsolateral PAG, but not the adjacent lateral and dorsomedial subregions, is a key center that integrates the behavioral response to acute psychological threatening stimuli. In this study, we tested whether, consistent with this hypothesis, activation of neurons in the dorsolateral PAG evokes a pattern of cardiovascular and respiratory responses that is distinct from that evoked from surrounding regions. Arterial pressure, heart rate, renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) were recorded simultaneously in urethane-anesthetized rats. Microinjections of very small amounts of d,l-homocysteic acid (750 pmol in 15 nl) were made in sites throughout the dorsomedial, dorsolateral, and lateral PAG subregions. Increases in RSNA of similar magnitude accompanied by small to moderate increases in arterial pressure and heart rate were evoked from all three PAG subregions. In contrast, large increases in both PNA burst rate (respiratory rate) and overall respiratory activity were evoked only from a highly circumscribed region that corresponded closely to the dorsolateral PAG subregion at an intermediate to caudal level. Within this region, the evoked increases in RSNA and respiratory activity were highly correlated (r = 0.914, P < 0.001), suggesting the possibility that a common population of "command neurons" within the dorsolateral PAG may generate both sympathetic and respiratory responses from this region.