Ventral tegmental area neurotensin signaling links the lateral hypothalamus to locomotor activity and striatal dopamine efflux in male mice

Endocrinology
Christa M PattersonMartin G Myers

Abstract

Projections from the lateral hypothalamic area (LHA) innervate components of the mesolimbic dopamine (MLDA) system, including the ventral tegmental area (VTA) and nucleus accumbens (NAc), to modulate motivation appropriately for physiologic state. Neurotensin (NT)-containing LHA neurons respond to multiple homeostatic challenges and project to the VTA, suggesting that these neurons could link such signals to MLDA function. Indeed, we found that pharmacogenetic activation of LHA NT neurons promoted prolonged DA-dependent locomotor activity and NAc DA efflux, suggesting the importance of VTA neurotransmitter release by LHA NT neurons for the control of MLDA function. Using a microdialysis-mass spectrometry technique that we developed to detect endogenous NT in extracellular fluid in the mouse brain, we found that activation of LHA NT cells acutely increased the extracellular concentration of NT (a known activator of VTA DA cells) in the VTA. In contrast to the prolonged elevation of extracellular NAc DA, however, VTA NT concentrations rapidly returned to baseline. Intra-VTA infusion of NT receptor antagonist abrogated the ability of LHA NT cells to increase extracellular DA in the NAc, demonstrating that VTA NT promotes NAc DA re...Continue Reading

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Citations

May 21, 2016·Frontiers in Computational Neuroscience·Shayan Tabe-Bordbar, Thomas J Anastasio
Sep 4, 2018·ELife·Ream Al-HasaniMichael R Bruchas
Mar 21, 2019·PLoS Biology·Fumito NaganumaRamalingam Vetrivelan
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Jun 16, 2016·The Journal of Physiology·Patricia BonnavionAlexander C Jackson
Jan 19, 2021·Endocrinology·Nadejda Bozadjieva-KramerJonathan N Flak
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Sep 7, 2021·Physiological Reviews·Alan G WattsWolfgang Langhans

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