Sensory Detection of Food Rapidly Modulates Arcuate Feeding Circuits

Chen, Yiming; Lin, Yen‐Chu; Kuo, Tzu-Wei; Knight, Zachary A.

doi:10.1016/j.cell.2015.01.033

Cited by 499 publications

(626 citation statements)

References 34 publications

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“…other deep networks, and are thought to represent network firing bursts (24)(25)(26). Using simultaneous electrical recordings and GCaMP6s imaging from the same GAD65 LH -GCaMP6s cells in vitro, we confirmed that GCaMP6s linearly reports spike firing rate (Fig.…”

Section: Resultssupporting

confidence: 65%

Orexin-driven GAD65 network of the lateral hypothalamus sets physical activity in mice

Kosse

Schöne

Bracey

et al. 2017

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

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Damage to the lateral hypothalamus (LH) causes profound physical inactivity in mammals. Several molecularly distinct types of LH neurons have been identified, including orexin cells and glutamic acid decarboxylase 65 (GAD65) cells, but their interplay in orchestrating physical activity is not fully understood. Here, using optogenetic circuit analysis and cell type-specific deep-brain recordings in behaving mice, we show that orexin cell activation rapidly recruits GAD65 LH neurons. We demonstrate that internally initiated GAD65 LH cell bursts precede and accompany spontaneous running bouts, that selective chemogenetic silencing of natural GAD65 LH cell activity depresses voluntary locomotion, and that GAD65 LH cell overactivation leads to hyperlocomotion. These results thus identify a molecularly distinct, orexin-activated LH submodule that governs physical activity in mice.T he lateral hypothalamus (LH) is thought to provide an essential drive for diverse vital behaviors, including locomotion. Peri-LH lesions in mammals disrupt context-appropriate physical activity, and are associated with the human disorder encephalitis lethargica, which has been noted to make humans "sit motionless. . .all day" (1-6). The LH is not a homogeneous entity, but contains many molecularly distinct classes of neurons that are thought to have different physiological roles (7). However, the interrelations of distinct LH cell classes in computing and driving context-appropriate physical activity are not fully understood.For example, LH neurons expressing orexins/hypocretins (8, 9) become activated in diverse stressful contexts, including acute auditory stimulation, hypoglycemia, hypercapnia, and physical capture (3, 9-13). Orexin LH cell activity may thus represent an important input variable for computing context-appropriate locomotor outputs (3,14), and orexin peptides have been proposed to increase arousal and locomotion by actions on extrahypothalamic projections to areas such as the locus coeruleus (15, 16). However, hypoactivity phenotypes caused by orexin LH cell deletion are milder than the hypoactivity phenotypes caused by broader LH lesions (1-3, 5, 12, 13, 17-19), whereas melanin-concentrating hormone LH (MCH LH ) cell deletion causes hyperactivity, implying that MCH LH cells suppress locomotion (20). These findings suggest that additional drivers of physical activity may exist in the LH.It was recently found that LH neurons expressing glutamic acid decarboxylase 65 (GAD65) are distinct from orexin and MCH neurons (21). We hypothesized that these cells may be a source of natural LH signals underlying normal levels of physical activity. Here, we investigate this hypothesis by using a combination of cell type-specific manipulation and recording techniques. We find that GAD65 LH cells operate as a stress-and orexin-activated LH module whose physiological activity is essential for normal locomotion, and whose hyperactivity causes hyperlocomotion. ResultsOrexin and Stress Rapidly Recruit GAD65 LH Neurons. To examine whether orex...

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Section: Resultssupporting

confidence: 65%

Orexin-driven GAD65 network of the lateral hypothalamus sets physical activity in mice

Kosse

Schöne

Bracey

et al. 2017

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

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“…A critical experiment is to determine whether leptin signaling only in AgRP neurons is sufficient to maintain fertility in Lep db/db mice. Fasting and starvation activate AgRP neurons (12,41) and Lep ob/ob mice lacking the ability to make leptin have high AgRP neuronal activity because leptin normally inhibits AgRP neuron activity (42). The activated AgRP neurons release AgRP, NPY, and GABA (11)(12)(13)(14).…”

Section: Discussionmentioning

confidence: 99%

AgRP to Kiss1 neuron signaling links nutritional state and fertility

Padilla

Qiu

Nestor

et al. 2017

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

174

171

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Mammalian reproductive function depends upon a neuroendocrine circuit that evokes the pulsatile release of gonadotropin hormones (luteinizing hormone and follicle-stimulating hormone) from the pituitary. This reproductive circuit is sensitive to metabolic perturbations. When challenged with starvation, insufficient energy reserves attenuate gonadotropin release, leading to infertility. The reproductive neuroendocrine circuit is well established, composed of two populations of kisspeptin-expressing neurons (located in the anteroventral periventricular hypothalamus, Kiss1AVPV, and arcuate hypothalamus, Kiss1ARH), which drive the pulsatile activity of gonadotropin-releasing hormone (GnRH) neurons. The reproductive axis is primarily regulated by gonadal steroid and circadian cues, but the starvation-sensitive input that inhibits this circuit during negative energy balance remains controversial. Agouti-related peptide (AgRP)-expressing neurons are activated during starvation and have been implicated in leptin-associated infertility. To test whether these neurons relay information to the reproductive circuit, we used AgRP-neuron ablation and optogenetics to explore connectivity in acute slice preparations. Stimulation of AgRP fibers revealed direct, inhibitory synaptic connections with Kiss1ARH and Kiss1AVPV neurons. In agreement with this finding, Kiss1ARH neurons received less presynaptic inhibition in the absence of AgRP neurons (neonatal toxin-induced ablation). To determine whether enhancing the activity of AgRP neurons is sufficient to attenuate fertility in vivo, we artificially activated them over a sustained period and monitored fertility. Chemogenetic activation with clozapine N-oxide resulted in delayed estrous cycles and decreased fertility. These findings are consistent with the idea that, during metabolic deficiency, AgRP signaling contributes to infertility by inhibiting Kiss1 neurons.

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“…The development of calcium fluorescent probes, especially the genetically encoded calcium indicators (GECIs) has promoted the optical imaging and recording methods of measuring calcium levels as the proxies of cell-type specific neuronal activities [13,[18][19][20]. Compared to electrophysiology and other sophisticated imaging methods [6,[37][38][39], the fiber photometry is easy, convenient, and stable for in vivo monitoring of population neuronal activities, especially in the deep brain regions such as the striatum, amygdala and hypothalamus.…”

Section: Conclusion and Discussionmentioning

confidence: 99%

“…As an alternative, fiber photometry provides the most sensitive and easiest way to record cell-type specific population neuronal activities of the deep brain structures in behaving animals [10][11][12][13][14][15][16][17][18][19][20]. It employs one multimode optical fiber implanted in the brain.…”

Section: Introductionmentioning

confidence: 99%

“…The genetically encoded calcium indicators (GECIs), such as GCaMP proteins [22], enable the photometry method to record the activity of genetically defined neuronal subclasses. Using fiber photometry, several groups have made exciting observations of neuronal activation patterns in the sensory and motor cortices [10][11][12][14][15][16], basal ganglia [13], dopamine reward system [18], feeding circuits [20], basal forebrain [19], and have proposed new theories in each of these research fields.…”

Section: Introductionmentioning

confidence: 99%

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Multi-channel fiber photometry for population neuronal activity recording

Guo

Zhou

Feng

et al. 2015

Biomed. Opt. Express

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Fiber photometry has become increasingly popular among neuroscientists as a convenient tool for the recording of genetically defined neuronal population in behaving animals. Here, we report the development of the multi-channel fiber photometry system to simultaneously monitor neural activities in several brain areas of an animal or in different animals. In this system, a galvano-mirror modulates and cyclically couples the excitation light to individual multimode optical fiber bundles. A single photodetector collects excited light and the configuration of fiber bundle assembly and the scanner determines the total channel number. We demonstrated that the system exhibited negligible crosstalk between channels and optical signals could be sampled simultaneously with a sample rate of at least 100 Hz for each channel, which is sufficient for recording calcium signals. Using this system, we successfully recorded GCaMP6 fluorescent signals from the bilateral barrel cortices of a head-restrained mouse in a dual-channel mode, and the orbitofrontal cortices of multiple freely moving mice in a triple-channel mode. The multi-channel fiber photometry system would be a valuable tool for simultaneous recordings of population activities in different brain areas of a given animal and different interacting individuals.

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Sensory Detection of Food Rapidly Modulates Arcuate Feeding Circuits

Cited by 499 publications

References 34 publications

Orexin-driven GAD65 network of the lateral hypothalamus sets physical activity in mice

Orexin-driven GAD65 network of the lateral hypothalamus sets physical activity in mice

AgRP to Kiss1 neuron signaling links nutritional state and fertility

Multi-channel fiber photometry for population neuronal activity recording

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