Article
Biochemistry & Molecular Biology
Maria Sotelo, Jean Tyan, Chelsea Markunas, Bibi A. Sulaman, Lorraine Horwitz, Hankyu Lee, Joshua G. Morrow, Gideon Rothschild, Bo Duan, Ada Eban-Rothschild
Summary: The transition from wakefulness to sleep involves specific behaviors, such as nest-building and grooming, which are associated with stereotypic electroencephalogram (EEG) patterns. The ability to build a nest promotes sleep initiation and consolidation, while the lack of nesting material disrupts sleep. Neuronal ensembles in the lateral hypothalamus regulate the motivation to engage in nest-building behavior and control sleep initiation and intensity.
Review
Neurosciences
Mark A. Rossi
Summary: The lateral hypothalamic area (LHA) regulates energy balance through complex connections with other brain regions, leveraging distinct neuron populations. Recent studies have identified at least 30 different LHA neuron types, some of which influence specific aspects of energy homeostasis. This review highlights the emerging evidence from cell-type-specific investigations and proposes outstanding questions for future research.
TRENDS IN NEUROSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Song-Yu Li, Jing-Juan Cao, Kang Tan, Liu Fan, Ya-Qian Wang, Zi-Xuan Shen, Shuai-Shuai Li, Chao Wu, Hui Zhou, Hua-Tai Xu
Summary: Food cues play a pivotal role in triggering physiological responses and have a critical impact on obesity risk. This study revealed the crucial role of corticotropin-releasing hormone (CRH)-expressing neurons in the lateral hypothalamic area in promoting feeding behaviors in mice. The research also identified downstream targets and emphasized the involvement of CRH neuropeptide in orchestrating this regulatory network.
Review
Neurosciences
Lukas T. Oesch, Antoine R. Adamantidis
Summary: This review focuses on the electrical activity of feeding-promoting cells in the lateral hypothalamus across different states of vigilance, with a specific emphasis on REM sleep and its role in brain plasticity related to energy homeostasis and behavioral optimization.
TRENDS IN NEUROSCIENCES
(2021)
Article
Endocrinology & Metabolism
Moonsun Sa, Eun-Seon Yoo, Wuhyun Koh, Mingu Gordon Park, Hyun-Jun Jang, Yong Ryoul Yang, Mridula Bhalla, Jae-Hun Lee, Jiwoon Lim, Woojin Won, Jea Kwon, Joon-Ho Kwon, Yejin Seong, Byungeun Kim, Heeyoung An, Seung Eun Lee, Ki Duk Park, Pann-Ghill Suh, Jong-Woo Sohn, C. Justin Lee
Summary: The authors identify a role for GABRA5 neurons in the lateral hypothalamus for energy balance regulation. Inhibiting these neurons increases weight gain and lipid accumulation through a process dependent on astrocytic GABA release.
Article
Endocrinology & Metabolism
Moonsun Sa, Eun-Seon Yoo, Wuhyun Koh, Mingu Gordon Park, Hyun-Jun Jang, Yong Ryoul Yang, Mridula Bhalla, Jae-Hun Lee, Jiwoon Lim, Woojin Won, Jea Kwon, Joon-Ho Kwon, Yejin Seong, Byungeun Kim, Heeyoung An, Seung Eun Lee, Ki Duk Park, Pann-Ghill Suh, Jong-Woo Sohn, C. Justin Lee
Summary: The study identifies GABRA5 neurons in the lateral hypothalamus as important regulators of energy balance. Inhibiting these neurons leads to increased weight gain and lipid accumulation, which is dependent on astrocytic GABA release.
Article
Neurosciences
Mark A. Rossi, Marcus L. Basiri, Yuejia Liu, Yoshiko Hashikawa, Koichi Hashikawa, Lief E. Fenno, Yoon Seok Kim, Charu Ramakrishnan, Karl Deisseroth, Garret D. Stuber
Summary: The lateral hypothalamic area (LHA) contains distinct populations of glutamatergic neurons that project to different brain regions, with neurons projecting to the lateral habenula (LHb) or ventral tegmental area (VTA) showing anatomical, transcriptional, electrophysiological, and functional differences. Neurons projecting to the LHb are particularly sensitive to satiety state and feeding hormones, indicating differential processing of reward and aversion stimuli in divergent efferent pathways.
Article
Cell Biology
Anne Petzold, Hanna Elin van den Munkhof, Rebecca Figge-Schlensok, Tatiana Korotkova
Summary: By studying freely behaving mice using calcium imaging, optogenetics, and chemogenetics, researchers found that two neuronal populations in the lateral hypothalamus guide hungry animals to make behavioral choices between nutritional and social rewards. One population of neurons increased food consumption by inhibiting hunger signals, while the other population limited feeding and drinking and promoted social interaction despite hunger or thirst. These findings shed light on the neuronal mechanisms of balancing competing needs and provide insights into the flexible fulfillment of essential needs in animals.
Article
Clinical Neurology
Matei Bolborea, Pauline Vercruysse, Tselmen Daria, Johanna C. Reiners, Najwa Ouali Alami, Simon J. Guillot, Stephane Dieterle, Jerome Sinniger, Jelena Scekic-Zahirovic, Amela Londo, Hippolyte Arcay, Marc-Antoine Goy, Claudia Nelson de Tapia, Dietmar R. Thal, Kazumoto Shibuya, Ryo Otani, Kimihito Arai, Satoshi Kuwabara, Albert C. Ludolph, Francesco Roselli, Deniz Yilmazer-Hanke, Luc Dupuis
Summary: Amyotrophic lateral sclerosis (ALS) is associated with impaired energy metabolism, including weight loss and decreased appetite. The neural mechanisms underlying metabolic impairment in ALS are not fully understood. This study found that hypothalamic atrophy occurs early in ALS patients. Loss of MCH-positive neurons was observed in mouse models of ALS, and supplementation with MCH led to weight gain and increased food intake in these mice. Moreover, pTDP-43 pathology and neurodegeneration were documented in the hypothalamus of ALS patients. These findings suggest that hypothalamic MCH loss contributes to the metabolic changes in ALS.
ACTA NEUROPATHOLOGICA
(2023)
Article
Neurosciences
Catherine S. Thomas, Aida Mohammadkhani, Madiha Rana, Min Qiao, Corey Baimel, Stephanie L. Borgland
Summary: Reward and reinforcement processes are critical for survival and propagation of genes, with mesolimbic dopamine playing a central role. Optogenetic stimulation of orexin/dynorphin inputs in the VTA potentiates dopamine release in the NAc core, resulting in real time and conditioned place preference as well as increased food cue-directed orientation. While dynorphin contributes to aversive conditioning, the rewarding effects of LH orexin/dynorphin stimulation in the VTA are primarily driven by orexin rather than dynorphin.
NEUROPSYCHOPHARMACOLOGY
(2022)
Review
Neurosciences
Cristina Concetti, Denis Burdakov
Summary: The lateral hypothalamus plays a role in sleep-wake control by producing orexin/hypocretin and melanin-concentrating hormone neuropeptides. These neuropeptides can rapidly change their firing in response to external stimuli in awake animals. Optogenetic and chemogenetic manipulations suggest that rapid lateral hypothalamic dynamics shape cognitive and motor processes in the awake brain.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Yao Wang, Rong Guo, Bo Chen, Tanbin Rahman, Li Cai, Yizhi Li, Yan Dong, George C. Tseng, Jidong Fang, Marianne L. Seney, Yanhua H. Huang
Summary: Cocaine withdrawal leads to gene expression and electrophysiological changes in melanin-concentrating hormone neurons in the lateral hypothalamus, affecting REM sleep. Stimulation of these neurons enhances REM sleep quality and quantity after long-term withdrawal.
MOLECULAR PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Ekaterina Martianova, Renata Sadretdinova, Alicia Pageau, Nikola Pausic, Tommy Doucet Gentiletti, Danahe Leblanc, Arturo Marroquin Rivera, Benoit Labonte, Christophe D. Proulx
Summary: The outputs of lateral hypothalamic neurons play a critical role in sensory integration and organizing behavior responses. This study demonstrates the significant coherent activity of three major neuronal outputs projecting to downstream targets during sensory-evoked or self-initiated motor responses in mice.
Article
Biochemistry & Molecular Biology
Junewoo Na, Byong Seo Park, Doohyeong Jang, Donggue Kim, Thai Hien Tu, Youngjae Ryu, Chang Man Ha, Marco Koch, Sungchil Yang, Jae Geun Kim, Sunggu Yang
Summary: This study extensively characterizes the AgRP, POMC, and dopaminergic neurons in the hypothalamic arcuate nucleus (Arc). The distinct anatomical and physiological properties of these neurons in response to appetite-regulating hormones are identified. This research highlights the importance of hypothalamic Arc neurons in appetite control.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Justin N. Siemian, Miguel A. Arenivar, Sarah Sarsfield, Cara B. Borja, Charity N. Russell, Yeka Aponte
Summary: Research shows that a subpopulation of LH GABAergic neurons expressing leptin receptors specifically drives appetitive behaviors in mice, while their ablation does not affect weight gain and food intake. Both groups of neurons in the LH can modulate reward-related behaviors, but only LHVGAT neurons impact feeding, and LHLEPR neurons can discriminate conditioned cues in Pavlovian paradigms.
Review
Neurosciences
Denis Burdakov
Review
Clinical Neurology
Claudio L. A. Bassetti, Antoine Adamantidis, Denis Burdakov, Fang Han, Steffen Gay, Ulf Kallweit, Ramin Khatami, Frits Koning, Brigitte R. Kornum, Gert Jan Lammers, Roland S. Liblau, Pierre H. Luppi, Geert Mayer, Thomas Pollmaecher, Takeshi Sakurai, Federica Sallusto, Thomas E. Scammell, Mehdi Tafti, Yves Dauvilliers
NATURE REVIEWS NEUROLOGY
(2019)
Review
Neurosciences
Mahesh M. Karnani, Cornelia Schone, Edward F. Bracey, J. Antonio Gonzalez, Paulius Viskaitis, Han-Tao Li, Antoine Adamantidis, Denis Burdakov
PROGRESS IN NEUROBIOLOGY
(2020)
Article
Neurosciences
Celia Garau, Craig Blomeley, Denis Burdakov
JOURNAL OF PHYSIOLOGY-LONDON
(2020)
Article
Biochemistry & Molecular Biology
Denis Burdakov, Mahesh M. Karnani
Article
Multidisciplinary Sciences
Cristina Concetti, Edward F. Bracey, Daria Peleg-Raibstein, Denis Burdakov
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Sivan Subburaju, Sarah Kaye, Yong Kee Choi, Jugajyoti Baruah, Debkanya Datta, Jun Ren, Ashwin Srinivasan Kumar, Gabor Szabo, Dai Fukumura, Rakesh K. Jain, Abdallah Elkhal, Anju Vasudevan
Article
Biochemistry & Molecular Biology
Paulius Viskaitis, Myrtha Arnold, Celia Garau, Lise T. Jensen, Lars Fugger, Daria Peleg-Raibstein, Denis Burdakov
Summary: Ingested non-essential amino acids activate hypothalamic orexin/hypocretin neurons and shift behavior from eating to exploration. This effect is independent of the gut/brain communication pathway. The study also suggests that the reduction in food intake caused by non-essential amino acids is related to the modulation of food palatability.
Article
Multidisciplinary Sciences
Han-Tao Li, Dane C. Donegan, Daria Peleg-Raibstein, Denis Burdakov
Summary: This study explores a deep brain stimulation (DBS) strategy for modulating anxiety symptoms by targeting the lateral hypothalamus (LH). The researchers identify a DBS waveform that inhibits anxiety-related neural activity and suppresses anxiety behaviors in mouse models without any noticeable side effects. These findings suggest that acute hypothalamic DBS could be a potential strategy for managing treatment-resistant anxiety disorders.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Nikola Grujic, Jeroen Brus, Denis Burdakov, Rafael Polania
Summary: This study reveals that mice exhibit rational behavior by adaptively allocating their sensory resources to maximize reward consumption in previously unexperienced environments. Despite imprecise perception of commonly occurring stimuli, this suggests awareness and efficient adaptation to neurocognitive limitations.
Review
Endocrinology & Metabolism
Daria Peleg-Raibstein, Paulius Viskaitis, Denis Burdakov
Summary: Seeking and ingesting nutrients is crucial for survival, but the classical behavioural sequence of seeking, ingesting, and resting may not be advantageous for all nutrients. Some nutrients are more essential for survival, and a key choice needs to be made after ingestion: to eat more and rest, or to terminate eating and search for better food. Recent research suggests that specific ingested macronutrients can rapidly and differentially modulate a group of neurons called hypothalamic hypocretin/orexin neurons (HONs), which promote explorative behaviors. This nutrient-specific modulation engages different reflex arcs: seek -> ingest -> seek and seek -> ingest -> rest.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Article
Neurosciences
Nikola Grujic, Alexander Tesmer, Ed Bracey, Daria Peleg-Raibstein, Denis Burdakov
Summary: This study reveals the involvement of orexin neurons in rapid arousal dynamics and reward perception. Pupil dilation, a quantitive arousal marker, is strongly correlated with orexin cell activity and is under their control. Orexin cells specialize in rapid and multiplexed communication of momentary arousal and reward states. The findings provide insights into the biological significance of eye pupil size.
NATURE NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Keshav S. Subramanian, Logan Tierno Lauer, Anna M. R. Hayes, Lea Decarie-Spain, Kara McBurnett, Anna C. Nourbash, Kristen N. Donohue, Alicia E. Kao, Alexander G. Bashaw, Denis Burdakov, Emily E. Noble, Lindsey A. Schier, Scott E. Kanoski
Summary: Food intake is regulated by both learned appetitive responses and physiological appetition signals. This study shows that melanin-concentrating hormone (MCH)-producing neurons in the lateral hypothalamic area (LHA) integrate these processes to promote caloric intake. The activity of MCH neurons is responsive to food-related cues and increases during eating, suggesting their involvement in the appetitive and consummatory processes.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Dane Donegan, Daria Peleg-Raibstein, Olivier Lambercy, Denis Burdakov
Summary: By studying the neural activation in the hypothalamus during premovement and its role in controlling adaptive movements, important insights into the behavioral and cognitive impact of neural signals are gained.