The gentle art of saying NO: how nitric oxide gets things done in the hypothalamus

The chemical signalling molecule nitric oxide (NO), which freely diffuses through aqueous and lipid environments, subserves an array of functions in the mammalian central nervous system, such as the regulation of synaptic plasticity, blood flow and neurohormone secretion. In this Review, we consider the cellular and molecular mechanisms by which NO evokes short-term and long-term changes in neuronal activity. We also highlight recent studies showing that discrete populations of neurons that synthesize NO in the hypothalamus constitute integrative systems that support life by relaying metabolic and gonadal signals to the neuroendocrine brain, and thus gate the onset of puberty and adult fertility. The putative involvement and therapeutic potential of NO in the pathophysiology of brain diseases, for which hormonal imbalances during postnatal development could be risk factors, is also discussed.