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Selective Restoration of Pomc Expression in Glutamatergic POMC Neurons: Evidence
for a Dynamic Hypothalamic Neurotransmitter Network.
Authors Jones GL, Wittmann G, Yokosawa EB, Yu H, Mercer AJ, Lechan RM, Low MJ
Submitted By Malcolm Low on 4/15/2019
Status Published
Journal eNeuro
Year 2019
Date Published 4/1/2019
Volume : Pages 6 : Not Specified
PubMed Reference 30957016
Abstract Hypothalamic POMC deficiency leads to obesity and metabolic deficiencies,
largely due to the loss of melanocortin peptides. However, POMC neurons in the
arcuate nucleus (ARC) are comprised of glutamatergic and GABAergic
subpopulations. The developmental program, relative proportion and function of
these two subpopulations are unresolved. To test whether glutamatergic POMC
neurons serve a distinct role in maintaining energy homeostasis, we activated
Pomc expression Cre- dependently in Vglut2-expressing neurons of mice with
conditionally silenced Pomc alleles. The Vglut2-Pomc restored mice had normal
ARC Pomc mRNA levels, POMC immunoreactivity, as well as body weight and body
composition at age 12 weeks. Unexpectedly, the cumulative total of Vglut2+
glutamatergic- and Gad67+ GABAergic-Pomc neurons detected by in situ
hybridization (ISH) exceeded 100% in both Vglut2- Pomc restored and control
mice, indicating that a subpopulation of Pomc neurons must express both neuronal
markers. Consistent with this hypothesis, triple ISH of C57BL/6J hypothalami
revealed that 35% of ARC Pomc neurons were selectively Gad67+, 21% were
selectively Vglut2+, and 38% expressed both Gad67 and Vglut2. The single Gad67+
and Vglut2+Pomc neurons were most prevalent in the rostral ARC, while the
Vglut2/Gad67+ dual-phenotype cells predominated in the caudal ARC. A lineage
trace using Ai9-tdTomato reporter mice to label fluorescently all
Vglut2-expressing neurons showed equal numbers of tdTomato+ and tdTomato- POMC
immunoreactive neurons. Together, these data suggest that POMC neurons exhibit
developmental plasticity in their expression of glutamatergic and GABAergic
markers, enabling re-establishment of normal energy homeostasis in the
Vglut2-Pomc restored mice.


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