Distinct Subsets of Lateral Hypothalamic Neurotensin Neurons are Activated by Leptin or Dehydration

Juliette A Brown,Anna Wright,David P Olson,Lyndsay Christensen,Gina M Leinninger,Raluca Bugescu

doi:10.1038/s41598-018-38143-9

Juliette A Brown, Anna Wright + Show 4 more

Open Access

https://doi.org/10.1038/s41598-018-38143-9

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Abstract

The lateral hypothalamic area (LHA) is essential for ingestive behavior but it remains unclear how LHA neurons coordinate feeding vs. drinking. Most LHA populations promote food and water consumption but LHA neurotensin (Nts) neurons preferentially induce water intake while suppressing feeding. We identified two molecularly and projection-specified subpopulations of LHA Nts neurons that are positioned to coordinate either feeding or drinking. One subpopulation co-expresses the long form of the leptin receptor (LepRb) and is activated by the anorectic hormone leptin (NtsLepRb neurons). A separate subpopulation lacks LepRb and is activated by dehydration (NtsDehy neurons). These molecularly distinct LHA Nts subpopulations also differ in connectivity: NtsLepRb neurons project to the ventral tegmental area and substantia nigra compacta but NtsDehy neurons do not. Intriguingly, the LHA Nts subpopulations cannot be discriminated via their classical neurotransmitter content, as we found that all LHA Nts neurons are GABAergic. Collectively, our data identify two molecularly- and projection-specified subpopulations of LHA Nts neurons that intercept either leptin or dehydration cues, and which conceivably could regulate feeding vs. drinking behavior. Selective regulation of these LHA Nts subpopulations might be useful to specialize treatment for ingestive disorders such as polydipsia or obesity.

Highlights

GABA neurons increases behaviors to obtain food and liquids, and invokes gnawing at non-caloric objects such as wood or the cage floor[18,19,20]; bulk activation of lateral hypothalamic area (LHA) GABA neurons cannot be considered to direct any specific ingestive behavior
We examined two brain regions that have been shown via Nts-In situ hybridization (ISH) to contain numerous Nts neurons: the subthalamic nucleus (STN) and the LHA36
We hypothesized that separate subpopulations of LHA Nts neurons might exist to coordinate opposing feeding and drinking behavior

Summary

Introduction

GABA neurons increases behaviors to obtain food and liquids, and invokes gnawing at non-caloric objects such as wood or the cage floor[18,19,20]; bulk activation of LHA GABA neurons cannot be considered to direct any specific ingestive behavior. Given that experimental activation of LHA Nts neurons promotes Nts release[24,27] and drinking[24,27,30,31], the dehydration-induced upregulation of LHA Nts could serve as a physiologic signal to drive water seeking and intake once water becomes available[32]. Taken together, these data suggest that some LHA Nts neurons can be activated by cues of energy or osmolality status and might comprise separate populations to coordinate feeding or drinking behavior. We assessed whether LHA NtsLepRb neurons and NtsDehy neurons are the same, or whether they are separate populations that are distinguishable via molecular, circuit and neurotransmitter criteria

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