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Review
. 2023 Jul:70:101069.
doi: 10.1016/j.yfrne.2023.101069. Epub 2023 May 5.

Fast neurotransmitter identity of MCH neurons: Do contents depend on context?

B G Beekly  1 , A Rupp  2 , C R Burgess  3 , C F Elias  4
Affiliations
Review

Fast neurotransmitter identity of MCH neurons: Do contents depend on context?

B G Beekly et al. Front Neuroendocrinol. 2023 Jul.

Abstract

Hypothalamic melanin-concentrating hormone (MCH) neurons participate in many fundamental neuroendocrine processes. While some of their effects can be attributed to MCH itself, others appear to depend on co-released neurotransmitters. Historically, the subject of fast neurotransmitter co-release from MCH neurons has been contentious, with data to support MCH neurons releasing GABA, glutamate, both, and neither. Rather than assuming a position in that debate, this review considers the evidence for all sides and presents an alternative explanation: neurochemical identity, including classical neurotransmitter content, is subject to change. With an emphasis on the variability of experimental details, we posit that MCH neurons may release GABA and/or glutamate at different points according to environmental and contextual factors. Through the lens of the MCH system, we offer evidence that the field of neuroendocrinology would benefit from a more nuanced and dynamic interpretation of neurotransmitter identity.

Keywords: GABA; Glutamate; Melanin-concentrating hormone; Neurodevelopment; Neurotransmitter switching; Sex variables.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1.
Fig. 1.
Different reporter genes and number of alleles with the transgene can affect results. (A) Fluorescent micrographs showing TdTomato expression in GHRH-Cre; TdTomato mouse. Note strong labeling of arcuate nucleus (ARH) neurons, tanycytes, and fibers projecting to the median eminence (ME). (B) Fluorescent micrographs showing eGFP-L10a expression in GHRH-Cre;eGFP-L10a mouse. Note only labeling of arcuate nucleus neurons. (C) Fluorescent micrographs showing TdTomato expression in a LepR-Cre;TdTomato mouse heterozygous for Cre. (D) Bright field micrographs showing leptin induced PSTAT3 expression. (E) Fluorescent micrographs showing TdTomato expression in LepR-Cre;TdTomato mouse homozygous for Cre. Abbreviations: ARH, arcuate nucleus of the hypothalamus; ME, median eminence; 3V, third ventricle.
Fig. 2.
Fig. 2.
MCH neuron transcriptome data from three published single-cell sequencing studies was further analyzed for genes associated with fast neurotransmission. (A) Visualization of dataset integration using the Seurat CCA approach. (B) Summary of major MCH neuron clusters. (C) Heat map of gene expression for the six clusters. Note that Cluster 1 is enriched for oligodendrocyte marker genes and is presumed to comprise MCH/oligodendrocyte doublets; Cluster 5 had few exclusive marker genes, poor integration, and low Pmch expression, and is thus presumed not to be a bona fide MCH neuron population; and Cluster 6 has few enriched markers and is presumed to comprise low read depth cells. (D) Bar graph displaying the breakdown of the percentage of MCH neurons in each cluster derived from each of the three analyzed datasets. (E) Pmch gene expression in each of the six clusters. Darker colors correspond to greater enrichment. (F-N) Expression of various fast neurotransmitter signaling machinery genes in each cluster. Darker colors correspond to greater enrichment.
See this image and copyright information in PMC

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