Cross-species analysis defines the conservation of anatomically segregated VMH neuron populations

Elife. 2021 May 21:10:e69065. doi: 10.7554/eLife.69065.

Abstract

The ventromedial hypothalamic nucleus (VMH) controls diverse behaviors and physiologic functions, suggesting the existence of multiple VMH neural subtypes with distinct functions. Combing translating ribosome affinity purification with RNA-sequencing (TRAP-seq) data with single-nucleus RNA-sequencing (snRNA-seq) data, we identified 24 mouse VMH neuron clusters. Further analysis, including snRNA-seq data from macaque tissue, defined a more tractable VMH parceling scheme consisting of six major genetically and anatomically differentiated VMH neuron classes with good cross-species conservation. In addition to two major ventrolateral classes, we identified three distinct classes of dorsomedial VMH neurons. Consistent with previously suggested unique roles for leptin receptor (Lepr)-expressing VMH neurons, Lepr expression marked a single dorsomedial class. We also identified a class of glutamatergic VMH neurons that resides in the tuberal region, anterolateral to the neuroanatomical core of the VMH. This atlas of conserved VMH neuron populations provides an unbiased starting point for the analysis of VMH circuitry and function.

Keywords: mouse; neuroscience; rhesus macaque; snRNA-seq; ventromedial hypothalamus.

Publication types

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

MeSH terms

  • Animals
  • Cluster Analysis
  • Databases, Genetic
  • Gene Expression Profiling
  • Genotype
  • Glutamic Acid / metabolism
  • Macaca mulatta
  • Mice, Transgenic
  • Multigene Family*
  • Neurons / metabolism
  • Neurons / physiology*
  • Phenotype
  • RNA-Seq
  • Receptors, Leptin / genetics
  • Receptors, Leptin / metabolism
  • Species Specificity
  • Steroidogenic Factor 1 / genetics
  • Steroidogenic Factor 1 / metabolism
  • Transcriptome*
  • Ventromedial Hypothalamic Nucleus / cytology
  • Ventromedial Hypothalamic Nucleus / metabolism
  • Ventromedial Hypothalamic Nucleus / physiology*

Substances

  • Receptors, Leptin
  • Steroidogenic Factor 1
  • leptin receptor, mouse
  • steroidogenic factor 1, mouse
  • Glutamic Acid

Associated data

  • GEO/GSE172207