Preferential development of neuropeptide Y/GABA circuit in hypothalamic arcuate nucleus in postnatal rats

The hypothalamus, which plays a critical role in regulation of energy homeostasis, is formed during the perinatal period and thus vulnerable to fetal/newborn environmental conditions. We investigated synaptogenesis and neurotransmission of neurons in arcuate nucleus of the hypothalamus (ARH) during the postnatal period using immunohistochemical and electrophysiological methods. Our results show that the density of neuropeptide Y (NPY) fibers increases abruptly after the second postnatal week. NPY and proopiomelanocortin (POMC) immunoreactive fibers/varicosities puncta are mutually juxtaposed to perikarya of both neurons with increasing NPY and decreasing POMC apposition until the third postnatal week. The frequencies of spontaneous GABAergic inhibitory and glutamatergic excitatory postsynaptic currents (sIPSC and sEPSC) increase with age, with action potential dependent sIPSCs predominant during first postnatal week and sEPSCs thereafter. The presynaptic function of ARH synapses appears to reach adult levels around the age of weaning, while the postsynaptic receptors are still undergoing modification, evidenced by changes of frequencies, amplitudes and deactivation kinetics of PSCs. The number of NPY fibers juxtaposed to NPY neurons is correlated with the frequency of postsynaptic currents, suggesting that NPY/GABA release may facilitate maturation of synapses on their innervated neurons. Our results indicate that a neural circuit in ARH with a stronger NPY/GABAergic tone undergoes significant development during the postnatal period, which may be important for the maturation and/or remodeling of ARH neural circuits.