Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes

Nat Neurosci. 2017 Feb;20(2):176-188. doi: 10.1038/nn.4462. Epub 2016 Dec 19.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism*
  • Dopaminergic Neurons / metabolism*
  • Hypothalamus / metabolism*
  • Immunohistochemistry / methods
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuropeptides / metabolism*
  • Neurotransmitter Agents / physiology
  • Suprachiasmatic Nucleus / metabolism
  • Synaptic Transmission / physiology
  • Tyrosine 3-Monooxygenase / metabolism*

Substances

  • Neuropeptides
  • Neurotransmitter Agents
  • neuromedin S
  • Tyrosine 3-Monooxygenase
  • Dopamine