Developmental switch in neuropeptide Y and melanocortin effects in the paraventricular nucleus of the hypothalamus.
Homeostatic regulation of energy balance in rodents changes dramatically during the first 3 postnatal weeks. Neuropeptide Y (NPY) and melanocortin neurons in the arcuate nucleus, a primary energy homeostatic center in adults, do not fully innervate the paraventricular nucleus (PVN) until the third postnatal week. We have identified two classes of PVN neurons responsive to these neuropeptides, tonically firing neurosecretory (NS) and burst-firing preautonomic (PA) cells. In neonates, NPY could inhibit GABAergic inputs to nearly all NS and PA neurons, while melanocortin regulation was minimal. However, there was a dramatic, age-dependent decrease in NPY responses specifically in the PA neurons, and a 3-fold increase in melanocortin responses in NS cells. These age-dependent changes were accompanied by changes in spontaneous GABAergic currents onto these neurons. This primarily NPYergic regulation in the neonates likely promotes the positive energy balance necessary for growth, while the developmental switch correlates with maturation of homeostatic regulation of energy balance.
Melnick
Igor
I
Department of Pharmacology, University of Alberta, Edmonton AB, T6G 2H7, Canada.
Pronchuk
Nina
N
Cowley
Michael A
MA
Grove
Kevin L
KL
Colmers
William F
WF
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D053486:Melanocortins / Q000494:pharmacology*; D009474:Neurons / Q000145:classification / Q000187:drug effects*; D009478:Neuropeptide Y / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013266:Stilbamidines / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D050485:GABA Plasma Membrane Transport Proteins; D053486:Melanocortins; D009478:Neuropeptide Y; D013266:Stilbamidines; D013973:Thyrotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone