GABAergic Projections from Lateral Hypothalamus to Paraventricular Hypothalamic Nucleus Promote Feeding

Wu, Zhaofei; Kim, E. R.; Sun, Hao; Xu, Yuanzhong; Mangieri, Leandra R.; Li, D.-P.; Pan, Hui Lin; Arenkiel, Benjamin R.; Tong, Qingchun

doi:10.1523/jneurosci.3720-14.2015

Cited by 81 publications

(78 citation statements)

References 33 publications

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“…3H ). Combined with our previous data on LH neurons (Wu et al, 2015), these data suggest that Pdx1-Cre targets a major subset of non-POMC, non-AgRP GABAergic neurons in the hypothalamus.…”

Section: Deletion Of Vgat By Pdx1-cre In the Hypothalamussupporting

confidence: 78%

“…7E), although the degree in difference was smaller than those observed in Pdx1-Cre:Vgat flox/flox mice. We previously reported that Sim1-Cre:␥2 flox/ flox mice exhibited reduced nocturnal feeding (Wu et al, 2015). Associated with this, these mice showed specific attenuation in O 2 consumption during the dark period (Fig.…”

Section: Disrupted Gabaergic Input To the Pvh Reduced Postweaning Gromentioning

confidence: 53%

“…We also included ISH for Vglut2 (also named Slc17a6 ), a marker for glutamatergic neurons, to serve as a control. Our previous results showed that Pdx1-Cre targets ϳ80% of GABAergic neurons in the LH (Wu et al, 2015). In addition to the LH of control mice, Vgat was also found to be abundantly expressed in the Arc (Fig.…”

Section: Deletion Of Vgat By Pdx1-cre In the Hypothalamusmentioning

confidence: 78%

“…We previously reported that mice lacking the ␥2-subunit in the PVH (Sim1-Cre:␥2 flox/flox mice) exhibited reduced feeding at 4 -5 weeks of age (Wu et al, 2015). The reduced nocturnal feeding supports that the PVH is one of the downstream targets that contribute significantly to the action of GABA released from Pdx1-Cre neurons.…”

Section: Disrupted Gabaergic Input To the Pvh Reduced Postweaning Gromentioning

confidence: 84%

“…Disruption of GABA release from hypothalamic non-POMC, non-AgRP neurons led to a reduction in postweaning and nocturnal feeding, suggesting that GABA release from these hypothalamic neurons is required to drive feeding. Among different hypothalamic regions with Pdx1-Cre expression, LH GABAergic neurons likely contribute significantly to feeding since specific disruption GABA release from LH neurons causes a reduction in feeding and is required for feeding driven by LH GABAergic neurons (Jennings et al, 2015;Wu et al, 2015). Our previous results on mice with almost complete Vgat deletion in the Arc show no obvious changes in feeding (Kong et al, 2012), arguing against a significant contribution of Arc non-POMC, non-AgRP neurons to the defect in postweaning feeding observed here.…”

Section: Discussionmentioning

confidence: 99%

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Hypothalamic Non-AgRP, Non-POMC GABAergic Neurons Are Required for Postweaning Feeding and NPY Hyperphagia

Kim

Sun

et al. 2015

Journal of Neuroscience

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The hypothalamus is critical for feeding and body weight regulation. Prevailing studies focus on hypothalamic neurons that are defined by selectively expressing transcription factors or neuropeptides including those expressing proopiomelanocortin (POMC) and agoutirelated peptides (AgRP). The Cre expression driven by the pancreas-duodenum homeobox 1 promoter is abundant in several hypothalamic nuclei but not in AgRP or POMC neurons. Using this line, we generated mice with disruption of GABA release from a major subset of non-POMC, non-AgRP GABAergic neurons in the hypothalamus. These mice exhibited a reduction in postweaning feeding and growth, and disrupted hyperphagic responses to NPY. Disruption of GABA release severely diminished GABAergic input to the paraventricular hypothalamic nucleus (PVH). Furthermore, disruption of GABA-A receptor function in the PVH also reduced postweaning feeding and blunted NPY-induced hyperphagia. Given the limited knowledge on postweaning feeding, our results are significant in identifying GABA release from a major subset of less appreciated hypothalamic neurons as a key mediator for postweaning feeding and NPY hyperphagia, and the PVH as one major downstream site that contributes significantly to the GABA action.

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“…3H ). Combined with our previous data on LH neurons (Wu et al, 2015), these data suggest that Pdx1-Cre targets a major subset of non-POMC, non-AgRP GABAergic neurons in the hypothalamus.…”

Section: Deletion Of Vgat By Pdx1-cre In the Hypothalamussupporting

confidence: 78%

Section: Disrupted Gabaergic Input To the Pvh Reduced Postweaning Gromentioning

confidence: 53%

Section: Deletion Of Vgat By Pdx1-cre In the Hypothalamusmentioning

confidence: 78%

Section: Disrupted Gabaergic Input To the Pvh Reduced Postweaning Gromentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Hypothalamic Non-AgRP, Non-POMC GABAergic Neurons Are Required for Postweaning Feeding and NPY Hyperphagia

Kim

Sun

et al. 2015

Journal of Neuroscience

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Xiaoyaosan regulates depression‐related behaviors with physical symptoms by modulating Orexin A/OxR1 in the hypothalamus

Hou

Liu

et al. 2020

The Anatomical Record

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The functional regulation of the orexin system in the central nervous system is closely related to the occurrence and development of psychotic disorders. Abnormal changes in the lateral region of the hypothalamus are associated with the comorbidity of depression and physical symptoms, and how the traditional Chinese formula Xiaoyaosan regulates these changes may reveal aspects of the pathogenesis of depression. This study aimed to establish a rat model of depression in order to examine changes in Orexin A/OxR1 expression in the lateral region of the hypothalamus and the effects of Xiaoyaosan. Sixty specific pathogen‐free (SPF) male healthy Sprague–Dawley (SD) rats were used in the experiment and randomly divided into the control group, the model group, the Xiaoyaosan group and the fluoxetine group. The depression model was established by 21‐day chronic immobilization stress (CIS). Food intake and body weight were recorded, and the sucrose preference test (SPT) and open field test (OFT) were used to evaluate the model. Then, the expression of Orexin A/OxR1 in the hypothalamus was measured by ELISA, Western blot and quantitative real‐time polymerase chain reaction (qRT‐PCR) analysis. The expression of Orexin A and OxR1 in the lateral hypothalamic area was significantly down regulated in the model group, compared with the control group. Xiaoyaosan significantly reversed these changes with obvious curative effects. Abnormal changes in Orexin A/OxR1 in the lateral hypothalamic area of rats with depression caused by chronic stress are closely related to the pathogenesis of depression accompanied by physical symptoms. Xiaoyaosan can improve depression accompanied by physical symptoms by regulating Orexin A/OxR1.

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Control of wakefulness by lateral hypothalamic glutamatergic neurons in male mice

Wang

Guo

Jiang

et al. 2021

J of Neuroscience Research

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The lateral hypothalamus (LH) plays a key role in the maintenance of cortical activation and wakefulness. In the LH, the two main neuronal cell populations consist of excitatory glutamatergic neurons and inhibitory GABAergic neurons. Recent studies have shown that inhibitory LH GABAergic neurons are wake-promoting. However, the mechanism by which excitatory LH glutamatergic neurons contribute to sleep-wake regulation remains unclear. Using fiber photometry in male mice, we demonstrated that LH glutamatergic neurons exhibited high activities during both wakefulness and rapid eye movement sleep. Chemogenetic activation of LH glutamatergic neurons induced an increase in wakefulness that lasted for 6 hr, whereas suppression of LH glutamatergic neuronal activity caused a reduction in wakefulness. Brief optogenetic activation of LH glutamatergic neurons induced an immediate transition from slowwave sleep to wakefulness, and long-lasting optogenetic stimulation of these neurons maintained wakefulness. Moreover, we found that LH-locus coeruleus/parabrachial nucleus and LH-basal forebrain projections mediated the wake-promoting effects of LH glutamatergic neurons. Taken together, our data indicate that LH glutamatergic neurons are essential for the induction and maintenance of wakefulness. The results presented here may advance our understanding of the role of LH in the control of wakefulness.

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GABAergic Projections from Lateral Hypothalamus to Paraventricular Hypothalamic Nucleus Promote Feeding

Cited by 81 publications

References 33 publications

Hypothalamic Non-AgRP, Non-POMC GABAergic Neurons Are Required for Postweaning Feeding and NPY Hyperphagia

Hypothalamic Non-AgRP, Non-POMC GABAergic Neurons Are Required for Postweaning Feeding and NPY Hyperphagia

Xiaoyaosan regulates depression‐related behaviors with physical symptoms by modulating Orexin A/OxR1 in the hypothalamus

Control of wakefulness by lateral hypothalamic glutamatergic neurons in male mice

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