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SUMMARYThe central amygdala (CeA) consists of numerous genetically-defined inhibitory neurons that control defensive and appetitive behaviors including feeding. Transcriptomic signatures of cell types and their links to function remain poorly understood. Using single-nucleus RNA-sequencing, we describe nine CeA cell clusters, of which four are mostly associated with appetitive and two with aversive behaviors. To analyze the activation mechanism of appetitive CeA neurons, we characterized Serotonin receptor 2a (Htr2a)-expressing neurons (CeAHtr2a) that comprise three appetitive clusters and were previously shown to promote feeding. In vivo calcium imaging revealed that CeAHtr2aneurons are activated by fasting, the hormone ghrelin, and the presence of food. Moreover, these neurons are required for the orexigenic effects of ghrelin. Appetitive CeA neurons responsive to fasting and ghrelin project to the parabrachial nucleus (PBN) causing inhibition of target PBN neurons. These results illustrate how the transcriptomic diversification of CeA neurons relates to fasting and hormone-regulated feeding behavior.HighlightsTranscriptomics reveals four appetitive, two aversive and three unknown CeA clustersGhrelin and fasting activate CeAHtr2aneurons comprising three appetitive clustersGhrelin’s orexigenic effects require the activity of appetitive CeA neuronsCeA-→PBN inhibition is necessary for ghrelin/fasting induced feeding