Topographic mapping of VMH --> arcuate nucleus microcircuits and their reorganization by fasting.
In the hypothalamic arcuate nucleus (ARC), pro-opiomelanocortin (POMC) neurons inhibit feeding and neuropeptide-Y (NPY) neurons stimulate feeding. We tested whether neurons in the ventromedial hypothalamic nucleus (VMH), a known satiety center, activate anorexigenic neuronal pathways in the ARC by projecting either excitatory synaptic inputs to POMC neurons and/or inhibitory inputs to NPY neurons. Using laser scanning photostimulation in brain slices from transgenic mice, we found that POMC and NPY neurons, which are interspersed in the ARC, are nevertheless regulated by anatomically distinct synaptic inputs. POMC neurons received strong excitatory input from the medial VMH (mVMH), whereas NPY neurons did not and, instead, received weak inhibitory input only from within the ARC. The strength of the excitatory input from the mVMH to POMC neurons was diminished by fasting. These data identify a new molecularly defined circuit that is dynamically regulated by nutritional state in a manner consistent with the known role of the VMH as a satiety center.
Sternson
Scott M
SM
Howard Hughes Medical Institute and Laboratory of Molecular Genetics, The Rockefeller University, 1230 York Ave., New York, New York 10021, USA.
Shepherd
Gordon M G
GM
Friedman
Jeffrey M
JM
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D000831:Animals, Newborn; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology*; D001931:Brain Mapping; D005215:Fasting; D018698:Glutamic Acid / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007834:Lasers; D020738:Leptin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000502:physiology*; D016571:Neural Networks, Computer; D009473:Neuronal Plasticity / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000502:physiology* / Q000528:radiation effects; D009478:Neuropeptide Y / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D010775:Photic Stimulation / Q000379:methods; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D013569:Synapses / Q000528:radiation effects
D020738:Leptin; D009478:Neuropeptide Y; D018698:Glutamic Acid; D011333:Pro-Opiomelanocortin