Arcuate Dopaminergic/GABAergic Neurons Project Within the Hypothalamus and to the Median Eminence

Authors

Somya Mittal
Benjamin R Arenkiel
Ariel M Lyons-Warren

Language

English

Publication Date

9-1-2024

Journal

Journal of Neurophysiology

DOI

10.1152/jn.00086.2024

PMID

39108212

PMCID

PMC11427037

PubMedCentral® Posted Date

8-7-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Cotransmission, meaning the release of multiple neurotransmitters from one synapse, allows for increased diversity of signaling in the brain. Dopamine (DA) and γ-aminobutyric acid (GABA) are known to coexpress in many regions such as the olfactory bulb and the ventral tegmental area. Tuberoinfundibular dopaminergic neurons (TIDA) in the arcuate nucleus of the hypothalamus (Arc) project to the median eminence (ME) and regulate prolactin release from the pituitary, and prior work suggests dopaminergic Arc neurons also cotransmit GABA. However, the extent of cotransmission, and the projection patterns of these neurons have not been fully revealed. Here, we used a genetic intersectional reporter expression approach to selectively label cells that express both tyrosine hydroxylase (TH) and vesicular GABA transporter (VGAT). Through this approach, we identified cells capable of both DA and GABA cotransmission in the Arc, periventricular (Pe), paraventricular (Pa), ventromedial, and the dorsolateral hypothalamic nuclei, in addition to a novel population in the caudate putamen. The highest density of labeled cells was in the Arc, 6.68% of DAPI-labeled cells at Bregma -2.06 mm, and in the Pe, 2.83% of DAPI-labeled cells at Bregma -1.94 mm. Next, we evaluated the projections of these DA/GABA cells by injecting an mCherry virus that fluoresces in DA/GABA cells. We observed a cotransmitting DA/GABA population, with projections within the Arc, and to the Pa and ME. These data suggest DA/GABA Arc neurons are involved in prolactin release as a subset of TIDA neurons. Further investigation will elucidate the interactions of dopamine and GABA in the hypothalamus.

NEW & NOTEWORTHY Cotransmitting dopaminergic (DA) and γ-aminobutyric acid (GABA)ergic (DA/GABA) neurons contribute to the complexity of neural circuits. Using a new genetic technique, we characterized the locations, density, and projections of hypothalamic DA/GABA neurons. DA/GABA cells are mostly in the arcuate nucleus (Arc), from which they project locally within the arcuate, to the median eminence (ME), and to the paraventricular (Pa) nucleus. There is also a small and previously unreported group of DA/GABA cells in the caudate putamen.

Keywords

Animals, Arcuate Nucleus of Hypothalamus, GABAergic Neurons, Median Eminence, Dopaminergic Neurons, Male, Mice, Tyrosine 3-Monooxygenase, Vesicular Inhibitory Amino Acid Transport Proteins, Female, Neural Pathways, arcuate nucleus, cotransmission, dopamine, GABA, hypothalamus

Published Open-Access

yes

Recommended Citation

Somya Mittal, Benjamin R Arenkiel, and Ariel M Lyons-Warren, "Arcuate Dopaminergic/GABAergic Neurons Project Within the Hypothalamus and to the Median Eminence" (2024). Duncan NRI Faculty and Staff Publications. 129.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/129