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.

Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin 2C receptor stimulation.

The dynamic interplay between serotonin [5-hydroxytryptamine (5-HT)] neurotransmission and the hypothalamic-pituitary-adrenal (HPA) axis has been extensively studied over the past 30 years, but the underlying mechanism of this interaction has not been defined. A possibility receiving little attention is that 5-HT regulates upstream corticotropin-releasing hormone (CRH) signaling systems via activation of serotonin 2C receptors (5-HT(2C)Rs) in the paraventricular nucleus of the hypothalamus (PVH). Through complementary approaches in wild-type rodents and 5-HT(2C)R-deficient mice, we determined that 5-HT(2C)Rs are necessary for 5-HT-induced HPA axis activation.

NPY presynaptic actions are reduced in the hypothalamic mpPVN of obese (fa/fa), but not lean, Zucker rats in vitro.

1. Neuropeptide Y (NPY) profoundly enhances feeding when injected intracerebroventricularly, or directly into hypothalamic nuclei, such as the paraventricular nucleus (PVN). Paradoxically, NPY has a reduced action on feeding in obese Zucker rats relative to lean Zucker rats, although the obese rats have much higher levels of hypothalamic NPY expression.

The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis.

The gastrointestinal peptide hormone ghrelin stimulates appetite in rodents and humans via hypothalamic actions. We discovered expression of ghrelin in a previously uncharacterized group of neurons adjacent to the third ventricle between the dorsal, ventral, paraventricular, and arcuate hypothalamic nuclei. These neurons send efferents onto key hypothalamic circuits, including those producing neuropeptide Y (NPY), Agouti-related protein (AGRP), proopiomelanocortin (POMC) products, and corticotropin-releasing hormone (CRH).

Multiple NPY receptors Inhibit GABA(A) synaptic responses of rat medial parvocellular effector neurons in the hypothalamic paraventricular nucleus.

We have recently shown that NPY and alpha-melanocyte-stimulating hormone, which potently induce or inhibit feeding, respectively, have opposing modulatory actions on GABAergic synapses in the medial parvocellular region of the paraventricular hypothalamic nucleus (mpPVN). Because this action might underlie the effects of NPY on feeding, we have examined the pharmacology of NPY responses using electrophysiological recordings. Focal electrical stimulation within the PVN elicited a GABA(A) synaptic response in some mpPVN neurons, which was reversibly inhibited by NPY in a concentration-dependent manner (EC(50) = 28 nM).