The hypothalamus contains the highest diversity of neurons in the brain. Many of these
neurons can co-release neurotransmitters and neuropeptides in a use-dependent manner.
Investigators have hitherto relied on candidate protein-based tools to correlate behavioral,
endocrine and gender traits with hypothalamic neuron identity. Here we map neuronal
identities in the hypothalamus by single-cell RNA sequencing. We distinguished 62
neuronal subtypes producing glutamatergic, dopaminergic or GABAergic markers for synaptic
neurotransmission and harboring the ability to engage in task-dependent neurotransmitter
switching. We identified dopamine neurons that uniquely coexpress the Onecut3 and
Nmur2 genes, and placed these in the periventricular nucleus with many synaptic afferents
arising from neuromedin S+ neurons of the suprachiasmatic nucleus. These neuroendocrine
dopamine cells may contribute to the dopaminergic inhibition of prolactin secretion
diurnally, as their neuromedin S+ inputs originate from neurons expressing Per2 and
Per3 and their tyrosine hydroxylase phosphorylation is regulated in a circadian fashion.
Overall, our catalog of neuronal subclasses provides new understanding of hypothalamic
organization and function.
