Regulation of Energy Expenditure by Brainstem GABA Neurons

Schneeberger, Marc; Parolari, Luca; Banerjee, Tania Das; Bhave, Varun; Wang, Putianqi; Patel, Bindiben; Topilko, Thomas; Wu, Zhuhao; Choi, Chan Hee J.; Yu, Xiaofei; Pellegrino, Kyle; Engel, Esteban A.; Cohen, Paul; Renier, Nicolas; Friedman, Jeffrey M.; Nectow, Alexander R.

doi:10.1016/j.cell.2019.05.048

Cited by 75 publications

(83 citation statements)

References 41 publications

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“…We began using an established FluoroGold (FG) retrograde tracing approach (16) combined with oxytocin antibody labeling (17,18) to carry out the first comprehensive quantification of the anatomical distribution and proportion of subtypes of OT neuron in the paraventricular nucleus (PVN) of the hypothalamus in male mice (postnatal day [30][31][32][33][34][35][36][37][38][39][40]. OT-Ab labeled neurons were classified as magnocellular if they were FG positive, and parvocellular if they were FG negative ( Fig.…”

mentioning

confidence: 99%

Parallel social information processing circuits are differentially impacted in autism

Lewis

Stein-O’Brien

Patino

et al. 2020

Preprint

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Parallel processing circuits are thought to dramatically expand the network capabilities of the nervous system. Magnocellular and parvocellular oxytocin neurons have been proposed to subserve two parallel streams of social information processing, which allow a single molecule to encode a diverse array of ethologically distinct behaviors, although to date direct evidence to support this hypothesis is lacking. Here we provide the first comprehensive characterization of magnocellular and parvocellular oxytocin neurons, validated across anatomical, projection target, electrophysiological, and transcriptional criteria. We next used novel multiple feature selection tools in Fmr1 KO mice to provide direct evidence that normal functioning of the parvocellular but not magnocellular oxytocin pathway is required for autism-relevant social reward behavior. Finally, we demonstrate that autism risk genes are uniquely enriched in parvocellular oxytocin neurons. Taken together these results provide the first evidence that oxytocin pathway specific pathogenic mechanisms account for social impairments across a broad range of autism etiologies.

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confidence: 99%

Parallel social information processing circuits are differentially impacted in autism

Lewis

Stein-O’Brien

Patino

et al. 2020

Preprint

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“…circuit in the regulation of energy expenditure. Schneeberger et al also found the opposing role of activation (decreased energy expenditure) associated with thermogenesis and locomotor activity, whereas inhibition (increased energy expenditure) was linked to only locomotor activity without any involvement of thermogenesis [96]. Serotonin, a prominent neurotransmitter in CNS, is also a major regulator of appetite and promotion of energy expenditure in addition to its association in behaviour and anxiety [97,98].…”

Section: Obesity and Satietymentioning

confidence: 99%

“…Recent studies have included a new brain region that might play a crucial role in the regulation of food intake and energy balance. In this context, Schneeberger et al described the role of GABAergic neurons in the dorsal raphe nucleus linked to the regulation of energy expenditure via interfering in locomotion and thermogenesis [96]. This information adds a new dimension for the role of dorsal raphe nucleus associated neuronal Int.…”

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confidence: 99%

Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity

Kumar

Singh

2020

IJMS

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Obesity is one of the major social and health problems globally and often associated with various other pathological conditions. In addition to unregulated eating behaviour, circulating peptide-mediated hormonal secretion and signaling pathways play a critical role in food intake induced obesity. Amongst the many peptides involved in the regulation of food-seeking behaviour, somatostatin (SST) is the one which plays a determinant role in the complex process of appetite. SST is involved in the regulation of release and secretion of other peptides, neuronal integrity, and hormonal regulation. Based on past and recent studies, SST might serve as a bridge between central and peripheral tissues with a significant impact on obesity-associated with food intake behaviour and energy expenditure. Here, we present a comprehensive review describing the role of SST in the modulation of multiple central and peripheral signaling molecules. In addition, we highlight recent progress and contribution of SST and its receptors in food-seeking behaviour, obesity (orexigenic), and satiety (anorexigenic) associated pathways and mechanism.Contrary to obesity, satiety is a sense of fullness due to ephemeral lack of interest in further ingestion of food, which eventually leads to the suppression of appetite. Fullness is supposed to have a vital role in weight management because it will impact the frequency and amount of food and drink consumed later [53]. The feeling of satiety is a well-organized and biologically oriented process [54,55]. Satiety is a well-articulated process which reduces gastric distension and cholecystokinin (CCK) release in gut post ingestion of nutrients and importantly has been associated with signals from periphery via vagal afferent fibers that terminate in nucleus of the tractus solitaries (NTS) in the brain stem [56]. Besides, leptin, a hormone secreted by adipocytes, is also associated with satiety signals and studies further indicate that satiety response to CCK that was blocked in leptin receptor-deficient rat was regained following restoration of the leptin receptor in arcuate nucleus (ARC) [57][58][59]. Studies also support the role of NTS vagus afferent in response to leptin [60,61]. Feeling satiated will, in the long run, smother the inclination for cravings and lead to lesser consumption of food in the next meal. Satiety is not a response; it involves a complex mechanism for its operation, which includes the crucial role of the hypothalamus and peripheral hormones and determines energy expenditure [62]. Measurement of satiation can be done either directly by assessing food intake or indirectly by subjectively rating the urge for appetite [63]. Schwartz et al. demonstrated that hypothalamus is the central brain region responsible for adiposity signal; however, it is not an active participant in satiety [64]. It is interesting to note that most satiety associated information is relayed to NTS afferent fibers from the vagus nerve and afferent from GIT through the spinal cord. Mechanical or chemical stimula...

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“…Volumetric imaging of stiff cleared samples and 3D registration to the Allen Brain Institute's Common Coordinate Framework (CCF) has eliminated the need to select individual tissue sections (Allen Institute for Brain Science, 2017). However, without a computational method for quantifying axon content, researchers must still select and score representative optical sections (Schneeberger et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Mapping Mesoscale Axonal Projections in the Mouse Brain Using A 3D Convolutional Network

Friedmann

Pun

Adams

et al. 2019

Preprint

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AbstractThe projection targets of a neuronal population are a key feature of its anatomical characterization. Historically, tissue sectioning, confocal microscopy, and manual scoring of specific regions of interest have been used to generate coarse summaries of mesoscale projectomes. We present here TrailMap, a 3D convolutional network for extracting axonal projections from intact cleared mouse brains imaged by light-sheet microscopy. TrailMap allows region-based quantification of total axon content in large and complex 3D structures after registration to a standard reference atlas. The identification of axonal structures as thin as one voxel benefits from data augmentation but also requires a loss function that tolerates errors in annotation. A network trained with volumes of serotonergic axons in all major brain regions can be generalized to map and quantify axons from thalamocortical, deep cerebellar, and cortical projection neurons, validating transfer learning as a tool to adapt the model to novel categories of axonal morphology. Speed of training, ease of use, and accuracy improve over existing tools without a need for specialized computing hardware. Given the recent emphasis on genetically and functionally defining cell types in neural circuit analysis, TrailMap will facilitate automated extraction and quantification of axons from these specific cell types at the scale of the entire mouse brain, an essential component of deciphering their connectivity.

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Regulation of Energy Expenditure by Brainstem GABA Neurons

Cited by 75 publications

References 41 publications

Parallel social information processing circuits are differentially impacted in autism

Parallel social information processing circuits are differentially impacted in autism

Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity

Mapping Mesoscale Axonal Projections in the Mouse Brain Using A 3D Convolutional Network

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