Systemic administration of leptin potentiates the response of neurons in the nucleus of the solitary tract to chemoreceptor activation in the rat.

Leptin microinjections into the nucleus of the solitary tract (NTS) have been shown to elicit sympathoexcitatory responses, and potentiate the cardiovascular responses to activation of the chemoreflex. In this study, experiments were done in Sprague-Dawley rats initially to provide a detailed mapping within the NTS complex of cells containing immunoreactivity to the long form of the leptin receptor (Ob-Rb). In a second series, this NTS region containing Ob-Rb immunoreactive cells was explored for single units antidromically activated by stimulation of pressor sites in the rostral ventrolateral medulla (RVLM). These antidromically identified neurons were then tested for their response to intra-carotid injections of leptin (50-100 ng/0.1 ml), and to activation of peripheral chemoreceptors following an injection of potassium cyanide (KCN) (80 μg/0.1 ml) into the carotid artery. Cells containing Ob-Rb-like immunoreactivity were found predominantly in the caudal NTS: within the medial, commissural and gelatinous (sub-postremal area) subnuclei of the NTS complex. Of 73 single units tested in these NTS regions, 48 were antidromically activated by stimulation of RVLM pressor sites and 25 of these single units responded with an increase in discharge rate after intra-carotid injections of leptin. In addition, 17 of these leptin responsive neurons were excited by the intra-carotid injections of KCN (80 μg/0.1 ml). Furthermore, the excitatory response of these single units to KCN was potentiated (59-83%) immediately following the leptin injection. These data indicate that leptin responsive neurons in NTS mediate chemoreceptor afferent information to pressor sites in the RVLM, and suggest that leptin may act as a facilitator on neuronal circuits within the NTS that potentiates the sympathoexcitatory responses elicited during the reflex activation of arterial chemoreceptors.