Histochemical Imaging of Brain Circuits that Regulate Food Intake

Abstract

We hypothesize that food intake during meals is regulated by a population of hypothalamic paraventricular (PVN) oxytocin (OXY) neurons that have direct projections to the nucleus tractus solitarius (NTS) in the hindbrain and enhance the behavioral and neuronal responses to cholecystokinin (CCK‐8), a satiety signal from the intestines. PVN OXY neurons terminate among NTS neurons that show Fos activation in response to CCK‐8. To identify OXY‐sensitive NTS neurons, we used laser capture microdissection (LCM) with RT‐PCR to demonstrate a reduction of neuropeptide Y (NPY) and OXY receptor (OXYr) mRNA in the NTS following injections of the neurotoxin OXY‐saporin. Retrograde tracer cholera toxin B injections into the NTS labeled OXY cells in the PVN. Fos immunoreactivity was increased in OXY PVN neurons following treatment with the adipocyte hormone leptin, which potentiates the satiety actions of CCK‐8 via CNS melanocortin‐4 receptors (MC4r). Using LCM and RT‐PCR, we identified MC4r mRNA in PVN neurons that project to the NTS. These findings indicate that leptin's anorectic actions in the CNS are mediated by MC4r signaling in PVN OXY neurons that project to the NTS in the hindbrain. Support: Dept. Veterans Affairs, NIH DK17047, DK52989, 5P30 DK35816‐18, NS32273, Advanced Targeting Systems.