Effects of GABA and Leptin Receptor‐Expressing Neurons in the Lateral Hypothalamus on Feeding, Locomotion, and Thermogenesis

Vrind, Véronne A J de; Rozeboom, Annemieke; Wolterink-Donselaar, Inge G.; Luijendijk-Berg, Mieneke C M; Adan, Roger A.H.

doi:10.1002/oby.22495

Cited by 33 publications

(35 citation statements)

References 41 publications

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“…Previous reports have shown that activation of GABA neurons in the LH increases food intake . Since our results showed that activation of GABA A receptors inhibited food intake, it is possible that stimulation of GABA A receptors reduces food intake by inhibition of GABA neurons in the LH.…”

Section: Discussionsupporting

confidence: 67%

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GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin

Yonemochi

Ardianto

Ueda

et al. 2019

Neuropsychopharm Rep

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Aim:The lateral hypothalamus (LH) is known as the hunger center, but the mechanisms through which the LH regulates food intake are unclear. Since GABA neurons are reported to project to the LH, the present study investigated the role of GABAergic function in the LH in the regulation of feeding behavior.Methods: GABA levels in the LH were measured by in vivo microdialysis. Food intake after drug injection into the LH was measured every 1 hour for 4 hours. The mRNA levels were measured using RT-PCR.Results: Food intake significantly increased GABA levels in the LH, suggesting that food intake stimulates GABAergic function in the LH. Injection of the GABA A receptor agonist muscimol into the LH significantly inhibited food intake, whereas injection of the GABA A receptor antagonist bicuculline into the LH did not significantly affect food intake. The inhibitory effect of muscimol injected into the LH was blocked by co-administration of bicuculline. These results indicate that the stimulation of GABA A receptors in the LH inhibits food intake. We next examined whether the stimulation of GABA A receptors affects hypothalamic neuropeptides that are known to regulate feeding behavior. The injection of muscimol significantly decreased preproorexin mRNA in the hypothalamus.

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Section: Discussionsupporting

confidence: 67%

“…However, most of these reports focused on GABA neurons in the LH. For instance, activation of GABA neurons in the LH increased food intake . More specifically, activation of GABA neurons projecting from the LH to the PVN increased food intake .…”

Section: Discussionmentioning

confidence: 98%

GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin

Yonemochi

Ardianto

Ueda

et al. 2019

Neuropsychopharm Rep

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“…A more recent study showed an increase in locomotion and decreased food intake during the dark cycle when chemogenetically activating LH LEPR neurons. Interestingly, the same study also showed that activation of the broader LH VGAT neuronal population decreased locomotor activity and increased food intake [49]. In contrast, ablation of LH GABA neurons did not cause locomotor deficits in mice when tested in an open field assay [20].…”

Section: Discussionmentioning

confidence: 99%

“…e . light versus dark cycles) may also account for the discrepancies observed in locomotion during chemogenetic [49] or optogenetic activation of LH LEPR neurons. Further work is needed to elucidate how the intersection of these factors may influence the contributions of LH LEPR neurons to behavior.…”

Section: Discussionmentioning

confidence: 99%

Activation of a lateral hypothalamic-ventral tegmental circuit gates motivation

et al. 2019

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Across species, motivated states such as food-seeking and consumption are essential for survival. The lateral hypothalamus (LH) is known to play a fundamental role in regulating feeding and reward-related behaviors. However, the contributions of neuronal subpopulations in the LH have not been thoroughly identified. Here we examine how lateral hypothalamic leptin receptor-expressing (LH LEPR ) neurons, a subset of GABAergic cells, regulate motivation in mice. We find that LH LEPR neuronal activation significantly increases progressive ratio (PR) performance, while inhibition decreases responding. Moreover, we mapped LH LEPR axonal projections and demonstrated that they target the ventral tegmental area (VTA), form functional inhibitory synapses with non-dopaminergic VTA neurons, and their activation promotes motivation for food. Finally, we find that LH LEPR neurons also regulate motivation to obtain water, suggesting that they may play a generalized role in motivation. Together, these results identify LH LEPR neurons as modulators within a hypothalamic-ventral tegmental circuit that gates motivation.

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“…The total LH GABA population promotes consummatory behaviors [102], while LH Gal neurons promote food-seeking [71]. However, LH LepR neuron activation decreases food intake and increases locomotion and body temperature [103], while intra-LH leptin injections decrease feeding and body weight [104]. Furthermore, intracerebroventricular leptin decreases the rewarding effect of LH stimulation [105], whereas chemogenetic activation of LH LepR neurons increases motivation for food [106].…”

Section: Leptin Receptor In the Hypothalamusmentioning

confidence: 99%

Molecular profiling and targeting of brain cells and circuits related to energy balance and food reward

Georgiadou¹

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In the great, grand scheme of things, we're just tiny specks that will one day be forgotten. So it doesn't matter what we did in the past or how we'll be remembered. The only thing that matters is right now, this moment. This one spectacular moment we are sharing together. Molecular profiling and genetic targeting of brain cells RNA sequencing for molecular profiling and classification of brain cells A popular and reliable method to investigate brain heterogeneity is RNA sequencing, which provides information about the whole transcriptome and can be applied to a brain region, a specific cell population or at the single cell level. Many different cell dissociation protocols and sequencing technologies exist, the application of which can vary depending on the brain region, cell abundance, developmental stage and the desired sequencing depth. For example, when researchers desire to sequence a particular cell type, they can use a transgenic animal expressing a fluorescent protein in the cell population of interest, Targeting neural subtypes and circuits with viral vectors Molecular profiling of cells is very useful for identifying novel cell types and gaining insights into their molecular makeup and transcriptional responses to cues. Nevertheless, in order to understand cell types better, we need to gain genetic access to them. A popular method for gene delivery into the brain in order to map cells, visualize brain connectivity and study the function of cell populations and circuits is viral vector technology. Viral vectors are used to target genetic information into cells of choice. To this end, either wild-type or engineered viral capsids are used to "package" the genetic information (transgene) designed in a way to facilitate proper expression of RNA or protein. Few of the most commonly used viral vectors in neuroscience are the adeno-associated virus (AAV), lentivirus (LV), canine adenovirus 2 (Cav2) and rabies. The two former are mostly used for anterograde targeting, while the two latter are used for retrograde targeting of neurons and are extremely useful for brain mapping of circuits. In this thesis we use AAV and Cav2, therefore we will discuss those. Adeno-associated viral vectors (AAVs) AAV is the most popular viral vector system used in neuroscience and gene therapy. The first gene therapy drug, which treats retinal dystrophy, was approved in 2017, while there are at least 20 approved gene therapy treatments available and at least 4000 ongoing clinical trials [25], [26]. Besides the fact that the AAV capsid has limited capacity and can accommodate only up to 5.2 kb of DNA, their use has a lot of advantages. Genes delivered by AAVs do not incorporate into the host genome and rather stay episomal [27], therefore they do not cause insertional mutations that could lead to toxic consequences. AAV capsids Hypothalamus, energy balance and leptin In this thesis we mostly focus on cells located in the hypothalamus (Chapters 1-3) and profile leptin receptor-expressing cells (Chapters 1 & 2). The hypothalamus is loc...

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Effects of GABA and Leptin Receptor‐Expressing Neurons in the Lateral Hypothalamus on Feeding, Locomotion, and Thermogenesis

Cited by 33 publications

References 41 publications

GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin

GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin

Activation of a lateral hypothalamic-ventral tegmental circuit gates motivation

Molecular profiling and targeting of brain cells and circuits related to energy balance and food reward

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