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

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

doi:10.1038/s41598-018-38143-9

Cited by 35 publications

(31 citation statements)

References 52 publications

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“…The LHA contains populations of neurons that promote fluid consumption. For example, activation of LHA neurotensin neurons promotes robust fluid consumption (76), although these neurons do not appear to project directly to the VTA (77). Alternatively, the lamina terminalis projects to LHA orexin neurons that, in turn, do project to the VTA and mediate waterdrinking behaviors (78).…”

Section: Discussionmentioning

confidence: 99%

Thirst recruits phasic dopamine signaling through subfornical organ neurons

Hsu

Bazzino

Hurh

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Thirst is a highly potent drive that motivates organisms to seek out and consume balance-restoring stimuli. The detection of dehydration is well understood and involves signals of peripheral origin and the sampling of internal milieu by first order homeostatic neurons within the lamina terminalis—particularly glutamatergic neurons of the subfornical organ expressing CaMKIIa (SFOCaMKIIa). However, it remains unknown whether mesolimbic dopamine pathways that are critical for motivation and reinforcement integrate information from these “early” dehydration signals. We used in vivo fiber photometry in the ventral tegmental area and measured phasic dopamine responses to a water-predictive cue. Thirst, but not hunger, potentiated the phasic dopamine response to the water cue. In euvolemic rats, the dipsogenic hormone angiotensin II, but not the orexigenic hormone ghrelin, potentiated the dopamine response similarly to that observed in water-deprived rats. Chemogenetic manipulations of SFOCaMKIIarevealed bidirectional control of phasic dopamine signaling during cued water reward. Taking advantage of within-subject designs, we found predictive relationships between changes in cue-evoked dopamine response and changes in behavioral responses—supporting a role for dopamine in motivation induced by homeostatic need. Collectively, we reveal a putative mechanism for the invigoration of goal-directed behavior: internal milieu communicates to first order, need state-selective circuits to potentiate the mesolimbic dopamine system’s response to cues predictive of restorative stimuli.

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Section: Discussionmentioning

confidence: 99%

Thirst recruits phasic dopamine signaling through subfornical organ neurons

Hsu

Bazzino

Hurh

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Given that this burst of drinking acutely increases weight, it may initially deter the weight loss effect of LHA Nts neurons. There are suggestions that LHA Nts-mediated suppression of feeding and promotion of drinking are regulated by different subsets of LHA Nts neurons and circuits ( 86 ). If true, it may be possible to selectively augment the “anorectic circuit” without invoking the “drinking circuit,” which could potentiate weight loss.…”

Section: Central Neurotensin Modulates Behaviors That Affect Body Weimentioning

confidence: 99%

“…It is equally possible that some LHA Nts neurons coordinate drinking and feeding suppression, such as dehydrated animals prioritizing water-seeking above feeding, termed dehydration anorexia . The increased Nts expression and neural activity observed within the LHA during dehydration anorexia suggests that LHA Nts neurons play an active role in coordinating osmotic status and ingestive behavior ( 86 , 87 ). It also remains to be determined how other transmitters expressed within LHA Nts neurons contribute to their function, including anorectic corticotropin-releasing hormone, or galanin and GABA implicated in promoting feeding via the LHA and VTA ( 88-91 ).…”

Section: Central Neurotensin Modulates Behaviors That Affect Body Weimentioning

confidence: 99%

The Role of Central Neurotensin in Regulating Feeding and Body Weight

Ramirez‐Virella

Leinninger

2021

Endocrinology

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The small peptide Neurotensin (Nts) is implicated in myriad processes including analgesia, thermoregulation, reward, arousal, blood pressure and modulation of feeding and body weight. Alterations in Nts have recently been described in individuals with obesity or eating disorders, suggesting that disrupted Nts signaling may contribute to body weight disturbance. Curiously, Nts mediates seemingly opposing regulation of body weight via different tissues. Peripherally-acting Nts promotes fat absorption and weight gain, while central Nts signaling suppresses feeding and weight gain. Thus, because Nts is pleiotropic, a location-based approach must be used to understand its contributions to disordered body weight and whether the Nts system might be leveraged to improve metabolic health. Here we review the role of Nts signaling in the brain to understand the sites, receptors and mechanisms by which Nts can promote behaviors that modify body weight. New techniques permitting site-specific modulation of Nts and Nts receptor- expressing cells suggest that, even in the brain, not all Nts circuitry exerts the same function. Intriguingly, there may be dedicated brain regions and circuits via which Nts specifically suppresses feeding behavior and weight gain vs. other Nts-attributed physiology. Defining the central mechanisms by which Nts signaling modifies body weight may suggest strategies to correct disrupted energy balance, as needed to address overweight, obesity and eating disorders.

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“…Optogenetic stimulation of A12 TH-positive cells evokes GABA responses in neighboring neurons in mouse brain slices (Zhang & van den Pol, 2015). In A13, Vglut2-mRNA is rare and VGAT mRNA is abundant (Brown et al, 2019), and…”

Section: Role Of Glutamatergic/da Transmission In Adultsmentioning

confidence: 99%

Heterogeneous expression of dopaminergic markers and Vglut2 in mouse mesodiencephalic dopaminergic nuclei A8–A13

Fougère

Zouwen

Boutin

et al. 2020

J of Comparative Neurology

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Co-transmission of glutamate by brain dopaminergic (DA) neurons was recently proposed as a potential factor influencing cell survival in models of Parkinson's disease. Intriguingly, brain DA nuclei are differentially affected in Parkinson's disease. Whether this is associated with different patterns of co-expression of the glutamatergic phenotype along the rostrocaudal brain axis is unknown in mammals. We hypothesized that, as in zebrafish, the glutamatergic phenotype is present preferentially in the caudal mesodiencephalic DA nuclei. Here, we used in mice a cell fate mapping strategy based on reporter protein expression (ZsGreen) consecutive to previous expression of the vesicular glutamate transporter 2 (Vglut2) gene, coupled with immunofluorescence experiments against tyrosine hydroxylase (TH) or dopamine transporter (DAT). We found three expression patterns in DA cells, organized along the rostrocaudal brain axis. The first pattern (TH-positive, DAT-positive, ZsGreenpositive) was found in A8-A10. The second pattern (TH-positive, DAT-negative, ZsGreen-positive) was found in A11. The third pattern (TH-positive, DAT-negative, ZsGreen-negative) was found in A12-A13. These patterns should help to refine the establishment of the homology of DA nuclei between vertebrate species. Our results also uncover that Vglut2 is expressed at some point during cell lifetime in DA nuclei known to degenerate in Parkinson's disease and largely absent from those that are preserved, suggesting that co-expression of the glutamatergic phenotype in DA cells influences their survival in Parkinson's disease.

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

Cited by 35 publications

References 52 publications

Thirst recruits phasic dopamine signaling through subfornical organ neurons

Thirst recruits phasic dopamine signaling through subfornical organ neurons

The Role of Central Neurotensin in Regulating Feeding and Body Weight

Heterogeneous expression of dopaminergic markers and Vglut2 in mouse mesodiencephalic dopaminergic nuclei A8–A13

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