ERC

The hypothalamus of the mammalian brain is an essential interface that decodes metabolic challenges through its fast-responding and functionally diverse neuronal populations. Hypothalamic neurons represent output stations under tight central regulation that, through their production of neuropeptides and hormones, orchestrate peripheral metabolic pathways. Despite intense research, distinguishing and rationalizing the molecular, morphological and functional diversity of hypothalamic neurons eluded investigators. Recently, we have established the single-cell transcriptome landscape of many hypothalamic nuclei, which we will use as a template to reveal the functional competence of novel cell identities. Our preliminary data distinguished 60 neuronal modalities; a level of neuronal heterogeneity that is unique to the brain. We will then focus on specific neuroendocrine subtypes to understand molecular rules of function determination. Particularly, we interrogate corticotropin-releasing hormone (CRH) release from the paraventricular nucleus since its pharmacological manipulation relieves stress. Lastly, we will analyze the role of hypothalamic centers in the molecular pathology of chronic adrenal insufficiency brought about by disrupted CRH production. Overall, our work program will produce new understanding on cellular diversity and organizational rules in the hypothalamus.