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Review
. 2020 Jan;32(1):e12801.
doi: 10.1111/jne.12801. Epub 2019 Dec 3.

Selective sexual differentiation of neurone populations may contribute to sex-specific outputs of the ventromedial nucleus of the hypothalamus

Laura G Kammel  1   2 , Stephanie M Correa  1
Affiliations
Review

Selective sexual differentiation of neurone populations may contribute to sex-specific outputs of the ventromedial nucleus of the hypothalamus

Laura G Kammel et al. J Neuroendocrinol. 2020 Jan.

Abstract

Sex differences among neurones in the ventrolateral region of the ventromedial hypothalamic nucleus (VMHvl) allow for the display of a diversity of sex-typical behaviours and physiological responses, ranging from mating behaviour to metabolism. Here, we review recent studies that interrogate the relationship between sex-typical responses and changes in cellular phenotypes. We discuss technologies that increase the resolution of molecular profiling or targeting of cell populations, including single-cell transcriptional profiling and conditional viral genetic approaches to manipulate neurone survival or activity. Overall, emerging studies indicate that sex-typical functions of the VMH may be mediated by phenotypically distinct and sexually differentiated neurone populations within the VMHvl. Future studies in this and other brain regions could exploit cell-type-specific tools to reveal the cell populations and molecular mediators that modulate sex-typical responses. Furthermore, cell-type-specific analyses of the effects of sexually differentiating factors, including sex hormones, can test the hypothesis that distinct cell types within a single brain region vary with respect to sexual differentiation.

Keywords: neuroactive steroids; neuropeptides; oestrogens; progestogens; steroids.

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Conflict of interest statement

The authors of the manuscript have no conflicts of interest to declare

Figures

Figure 1.
Figure 1.
Schematic depiction of three types of sex differences in the VMH. Sex differences in molecular phenotype (gene expression), cytoarchitecture (cell body size, synaptic density in response to estradiol), and circuit connectivity (afferent and efferent projections) are thought to contribute to sex-typical functions, including behavioral and physiological outputs.
Figure 2.
Figure 2.
Single cell RNA sequencing (scRNA-Seq) and viral genetic tools can help identify the molecular phenotype of sexually differentiated neuronal populations within the VMH and determine their contribution to VMH-mediated functions. A. Pipeline for scRNA-Seq of VMH neurons as reported in. Briefly, fluorescently labeled VMH neurons are isolated. A single-cell suspension allows for the transcriptome of individual cells to be analyzed. This approach revealed 6 molecularly distinct populations of neurons in the VMH. Figure adapted from. B. Viral genetic tools that manipulate neuronal survival or activity patterns can be used to determine cellular function. Top row, injection of Cre-dependent Caspase-3 AAV virus allows for cell-autonomous apoptosis (cell death) of specific neurons within the VMH. Middle row, injection of Cre-dependent DREADD AAV (eg. hM3Dq, hM4Di) allows for chemogenetic activation or inhibition of neuronal activity within VMH neurons following delivery of clozapine-N-oxide (CNO). Bottom row, injection of Cre-dependent optogenetic AAV (eg. ChR2, NpHr) allows for optogenetic activation or inhibition of VMH neurons via fiber photometry.
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