Dorsomedial hypothalamic nucleus neurons integrate important peripheral feeding-related signals in rats

Several studies have implicated the dorsomedial hypothalamic nucleus (DMN) in regulation of feeding behavior and body weight, but clear mechanisms by which it controls food intake are not well understood. We report the results of the present study, which showed that the DMN receives important peripheral short- and long-term feeding-related afferent signals, including gastric vagal, glycemia, and cholecystokinin (CCK) inputs, as well as from leptin, an adipostatic signal that forcefully inhibits food intake and increases metabolic rate. Among the 279 DMN neurons recorded, 173 (62.0%) responded to stimulation of gastric vagal nerves. Also, of the 123 DMN neurons responsive to gastric vagal stimulation that were tested with the administration of intravenous glucose, 75 (61.0%) were identified as being glycemia sensitive. Moreover, it is noteworthy that of the 23 DMN neurons that responded to both gastric vagal and intravenous glucose stimulation, most (19 of 23, 82.6%) were sensitive to circulating leptin, and some neurons (n = 7) were also responsive to systemic CCK, suggesting that gastric vagal, glycemic, CCK, and leptin inputs converge on single DMN neurons. Furthermore, synergistic interactions between leptin and glucose on single DMN neurons were observed (n = 6). These results demonstrate that those important peripheral feeding-related gastric vagal, glycemic, CCK and leptin signals not only reach the DMN but also interact on single DMN neurons, suggesting that the DMN may not just function as a relay station, but independently integrate the short-term and long-term feeding-associated information and actively participate in the direct regulation of feeding behavior.