Hypothalamic arcuate nucleus tyrosine hydroxylase neurons play orexigenic role in energy homeostasis

Energy homeostasis, food intake, and body weight are regulated by specific brain circuits. Here we introduce an unexpected neuron, the tyrosine hydroxylase (TH) neuron of the arcuate nucleus (ARC), that we show makes an orexigenic contribution. Optogenetic stimulation of mouse ARC TH neurons increased food intake; attenuating transmitter release reduced body weight. Optogenetic stimulation of ARC TH cells inhibited pro-opiomelanocortin (POMC) neurons through synaptic mechanisms. ARC TH cells project to the hypothalamic paraventricular nucleus; optogenetic stimulation of ARC TH axons inhibited paraventricular nucleus neurons by dopamine and GABA co-release. Dopamine excited orexigenic neurons that synthesize agouti-related peptide and neuropeptide Y but inhibited anorexigenic neurons that synthesize POMC, as determined by whole cell recording. Food deprivation increased c-fos expression and spike frequency in ARC TH neurons. The gut peptide ghrelin evoked direct excitatory effects, suggesting these neurons monitor metabolic cues. Together these data support the view that ARC TH cells play an unrecognized and influential positive role in energy homeostasis.