CCK-sensitive C fibers activate NTS leptin receptor-expressing neurons via NMDA receptors

Am J Physiol Regul Integr Comp Physiol. 2023 Dec 18. doi: 10.1152/ajpregu.00238.2022. Online ahead of print.ABSTRACTThe hormone leptin reduces food intake through actions in the peripheral and central nervous system, including in the hindbrain nucleus of the solitary tract (NTS). The NTS receives viscerosensory information via vagal afferents, including information from the gastrointestinal tract, which is then relayed to other CNS sites critical for control of food intake. Leptin receptors (lepRs) are expressed by a subpopulation of NTS neurons, and knockdown of these receptors increases both food intake and body weight. Recently, we demonstrated that leptin increases vagal activation of lepR-expressing neurons via increased NMDAR currents, thereby potentiating vagally-evoked firing. Furthermore, chemogenetic activation of these neurons was recently shown to inhibit food intake. However, the vagal inputs these neurons receive had not been characterized. Here we performed whole-cell recordings in brain slices taken from lepRCre X floxedTdTomato mice and found that lepR neurons of the NTS are directly activated by monosynaptic inputs from C-type afferents sensitive to the TRPV1 agonist capsaicin. CCK administered onto NTS slices stimulated spontaneous glutamate release onto lepR neurons and induced action potential firing; an effect mediated by CCKR1. Interestingly, NMDAR activation contributed to the current carried by spontaneous EPSCs and enhanced CCK-induced firing. Periph...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Source Type: research