Neurons for hunger and thirst transmit a negative-valence teaching signal
Open accessAbstract
Homeostasis is a biological principle for regulation of essential physiological parameters within a set range. Behavioural responses due to deviation from homeostasis are critical for survival, but motivational processes engaged by physiological need states are incompletely understood. We examined motivational characteristics of two separate neuron populations that regulate energy and fluid homeostasis by using cell-type-specific activity manipulations in mice. We found that starvation-sensitive AGRP neurons exhibit properties consistent with a negative-valence teaching signal. Mice avoided activation of AGRP neurons, indicating that AGRP neuron activity has negative valence. AGRP neuron inhibition conditioned preference for flavours and places. Correspondingly, deep-brain calcium imaging revealed that AGRP neuron activity rapidly reduced in response to food-related cues. Complementary experiments activating thirst-promoting neurons also conditioned avoidance. Therefore, these need-sensing neurons condition preference for environmental cues associated with nutrient or water ingestion, which is learned through reduction of negative-valence signals during restoration of homeostasis.
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AgRP and NOS1 neurons show heightened activity during hunger and thirst, their activity elicits an aversive state, and they are essential for driving feeding and drinking behaviors.
“A potentially similar function has been described for arcuate nucleus AgRP neurons and nitric oxide synthase 1 (NOS1) neurons in the subfornical organ (SFO). These neurons show heightened activity during hunger (AgRP) and thirst (NOS1), their activity elicits an aversive state (place avoidance), and they are essential for driving feeding and drinking behaviors, respectively21,227.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [227]
AgRP activity is rapidly suppressed on sensory detection of food, suggesting that ongoing AgRP activity is dispensable for food consumption.
“However, AgRP activity is rapidly suppressed on sensory detection of food227,228,230, which, surprisingly, suggests that ongoing AgRP activity is dispensable for food consumption.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [227]
AgRP neurons are activated in energy deficit, and their optical stimulation promotes food consumption but also elicits real-time place avoidance in the absence of food.
“AgRP neurons are activated in a state of energy deficit228, and their optical stimulation can voraciously promote food consumption, but also elicits real-time place avoidance (indicative of an aversive state) in the absence of food173,227,229.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [227]
A mouse may subsequently avoid a flavor that was paired with the AgRP neuronal stimulation that made it eat, leading some authors to suggest that stimulated hunger is necessarily an aversive drive that the mouse later associates with the flavor.
“However, a mouse may subsequently avoid a flavor that was paired with the AgRP neuronal stimulation that made it eat, leading some authors to suggest that stimulated hunger is necessarily an aversive drive that the mouse later associates with the flavor (Betley et al., 2015).”
From Evolving Concepts of Emotion and Motivation (2018) · cites this paper as Betley et al., 2015
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Cites
Ultrasensitive fluorescent proteins for imaging neuronal activity
Chen, T.-W., Wardill, T. J., Sun, Y., Pulver, S. R., Renninger, S. L., Baohan, A., Schreiter, E. R., Kerr, R. A., Orger, M. B., Jayaraman, V., et al. (2013) · Nature · doi:10.1038/nature12354 · Cited by 6,474 · see citing works
Avants, B., Epstein, C. L., Grossman, M., & Gee, J. C. (2007) · Medical Image Analysis · doi:10.1016/j.media.2007.06.004 · Cited by 5,618 · see citing works
Skinner, B. F., & Hull, C. L. (1944) · The American Journal of Psychology · doi:10.2307/1416955 · Cited by 4,061 · see citing works
THE BIOLOGY OF HUMAN STARVATION
Keys, A., BROŽEK, J., & Henschel, A. (1951) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.1951.tb56499.x · Cited by 2,053 · see citing works
The Biology of Human Starvation: Volume I
KEYS, A., BROŽEK, J., HENSCHEL, A., MICKELSEN, O., & TAYLOR, H. L. (1950) · doi:10.5749/j.ctv9b2tqv · Cited by 2,039 · see citing works
Rapid, reversible activation of AgRP neurons drives feeding behavior in mice
Krashes, M. J., Koda, S., Ye, C., Rogan, S. C., Adams, A. C., Cusher, D. S., Maratos-Flier, E., Roth, B. L., & Lowell, B. B. (2011) · Journal of Clinical Investigation · doi:10.1172/jci46229 · Cited by 1,578 · see citing works
Cabanac, M. (1971) · Science · doi:10.1126/science.173.4002.1103 · Cited by 1,521 · see citing works
Two-process learning theory: Relationships between Pavlovian conditioning and instrumental learning.
Rescorla, R. A., & Solomon, R. L. (1967) · Psychological Review · doi:10.1037/h0024475 · Cited by 1,487 · see citing works
Conditioning and Associative Learning
Hill, W. F., & Mackintosh, N. J. (1984) · The American Journal of Psychology · doi:10.2307/1422540 · Cited by 1,323 · see citing works
Motivation concepts in behavioral neuroscience
Berridge, K. C. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.02.004 · Cited by 1,302 · see citing works
Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning
Tsai, H.-C., Zhang, F., Adamantidis, A., Stuber, G. D., Bonci, A., de Lecea, L., & Deisseroth, K. (2009) · Science · doi:10.1126/science.1168878 · Cited by 1,266 · see citing works
AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training
Aponte, Y., Atasoy, D., & Sternson, S. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2739 · Cited by 1,157 · see citing works
Self-citationMiniaturized integration of a fluorescence microscope
Ghosh, K. K., Burns, L. D., Cocker, E. D., Nimmerjahn, A., Ziv, Y., Gamal, A. E., & Schnitzer, M. J. (2011) · Nature Methods · doi:10.1038/nmeth.1694 · Cited by 1,130 · see citing works
NPY/AgRP Neurons Are Essential for Feeding in Adult Mice but Can Be Ablated in Neonates
Luquet, S. H., Perez, F. A., Hnasko, T. S., & Palmiter, R. D. (2005) · Science · doi:10.1126/science.1115524 · Cited by 1,127 · see citing works
Saper, C. B., Chou, T. C., & Elmquist, J. K. (2002) · Neuron · doi:10.1016/s0896-6273(02)00969-8 · Cited by 1,120 · see citing works
Deconstruction of a neural circuit for hunger
Atasoy, D., Betley, J. N., Su, H. H., & Sternson, S. M. (2012) · Nature · doi:10.1038/nature11270 · Cited by 969 · see citing works
Self-citationHigh-throughput ethomics in large groups of Drosophila
Branson, K. M., Robie, A. A., Bender, J. A., Perona, P., & Dickinson, M. H. (2009) · Nature Methods · doi:10.1038/nmeth.1328 · Cited by 781 · see citing works
Automated Analysis of Cellular Signals from Large-Scale Calcium Imaging Data
Mukamel, E. A., Nimmerjahn, A., & Schnitzer, M. J. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.009 · Cited by 711 · see citing works
Avoidance Conditioning with Brief Shock and No Exteroceptive Warning Signal
Sidman, M. (1953) · Science · doi:10.1126/science.118.3058.157 · Cited by 663 · see citing works
Sensory Detection of Food Rapidly Modulates Arcuate Feeding Circuits
Chen, Y., Lin, Y.-C., Kuo, T.-W., & Knight, Z. A. (2015) · Cell · doi:10.1016/j.cell.2015.01.033 · Cited by 660 · see citing works
Atasoy, D., Aponte, Y., Su, H. H., & Sternson, S. M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1954-08.2008 · Cited by 614 · see citing works
Self-citationAn excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger
Krashes, M. J., Shah, B. P., Madara, J. C., Olson, D. P., Strochlic, D. E., Garfield, A. S., Vong, L., Pei, H., Watabe-Uchida, M., Uchida, N., et al. (2014) · Nature · doi:10.1038/nature12956 · Cited by 603 · see citing works
Parallel, Redundant Circuit Organization for Homeostatic Control of Feeding Behavior
Betley, J. N., Cao, Z. F. H., Ritola, K., & Sternson, S. M. (2013) · Cell · doi:10.1016/j.cell.2013.11.002 · Cited by 591 · see citing works
Self-citationSTEVENS' HANDBOOK OF EXPERIMENTAL PSYCHOLOGY
Pashler, H. (2002) · Wiley eBooks · doi:10.1002/0471214426 · Cited by 576 · see citing works
Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance
Stamatakis, A. M., & Stuber, G. D. (2012) · Nature Neuroscience · doi:10.1038/nn.3145 · Cited by 564 · see citing works
Visualizing Hypothalamic Network Dynamics for Appetitive and Consummatory Behaviors
Jennings, J. H., Ung, R. L., Resendez, S. L., Stamatakis, A. M., Taylor, J. G., Huang, J. H., Veleta, K., Kantak, P. A., Aita, M., Shilling-Scrivo, K. V., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.026 · Cited by 547 · see citing works
The Inhibitory Circuit Architecture of the Lateral Hypothalamus Orchestrates Feeding
Jennings, J. H., Rizzi, G., Stamatakis, A. M., Ung, R. L., & Stuber, G. D. (2013) · Science · doi:10.1126/science.1241812 · Cited by 493 · see citing works
Hunger States Switch a Flip-Flop Memory Circuit via a Synaptic AMPK-Dependent Positive Feedback Loop
Yang, Y., Atasoy, D., Su, H. H., & Sternson, S. M. (2011) · Cell · doi:10.1016/j.cell.2011.07.039 · Cited by 439 · see citing works
Self-citationOrexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus
van den Top, M., Lee, K., Whyment, A. D., Blanks, A. M., & Spanswick, D. (2004) · Nature Neuroscience · doi:10.1038/nn1226 · Cited by 435 · see citing works
Krashes, M. J., Shah, B. P., Koda, S., & Lowell, B. B. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.009 · Cited by 376 · see citing works
PRECLINICAL STUDY: FULL ARTICLE: Ghrelin increases intake of rewarding food in rodents
Egecioglu, E., Jerlhag, E., Salomé, N., Skibicka, K. P., Haage, D., Bohlooly‐Y, M., Andersson, D. R., Bjursell, M., Perrissoud, D., Engel, J. A., et al. (2010) · Addiction Biology · doi:10.1111/j.1369-1600.2010.00216.x · Cited by 332 · see citing works
Identical "Feeding" and "Rewarding" Systems in the Lateral Hypothalamus of Rats
Margules, D. L., & Olds, J. (1962) · Science · doi:10.1126/science.135.3501.374 · Cited by 328 · see citing works
Hagan, M. M., Rushing, P. A., Pritchard, L. M., Schwartz, M. W., Strack, A. M., der Ploeg, L. H. T. V., Woods, S. C., & Seeley, R. J. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.279.1.r47 · Cited by 320 · see citing works
Instant transformation of learned repulsion into motivational “wanting”
Robinson, M. J. F., & Berridge, K. C. (2013) · Current Biology · doi:10.1016/j.cub.2013.01.016 · Cited by 320 · see citing works
Navratilova, E., Xie, J. Y., Okun, A., Qu, C., Eyde, N., Ci, S., Ossipov, M. H., King, T., Fields, H. L., & Porreca, F. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214605109 · Cited by 313 · see citing works
Hypothalamic Survival Circuits: Blueprints for Purposive Behaviors
Sternson, S. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.018 · Cited by 313 · see citing works
Self-citationTakahashi, K. A., & Cone, R. D. (2005) · Endocrinology · doi:10.1210/en.2004-1397 · Cited by 308 · see citing works
Chemical and Genetic Engineering of Selective Ion Channel–Ligand Interactions
Magnus, C. J., Lee, P. H., Atasoy, D., Su, H. H., Looger, L. L., & Sternson, S. M. (2011) · Science · doi:10.1126/science.1206606 · Cited by 296 · see citing works
Self-citationArcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin
Wang, Q., Liu, C., Uchida, A., Chuang, J.-C., Walker, A. K., Liu, T., Osborne-Lawrence, S. L., Mason, B. L., Mosher, C. A., Berglund, E. D., et al. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.10.001 · Cited by 246 · see citing works
Thirst driving and suppressing signals encoded by distinct neural populations in the brain
Oka, Y., Ye, M., & Zuker, C. S. (2015) · Nature · doi:10.1038/nature14108 · Cited by 241 · see citing works
Leptin regulates the reward value of nutrient
Domingos, A. I., Vaynshteyn, J., Voss, H. U., Ren, X., Gradinaru, V., Zang, F., Deisseroth, K. A., de Araújo, I. E., & Friedman, J. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2977 · Cited by 230 · see citing works
Thirst following water deprivation in humans
Rolls, B. J., Wood, R. J., Rolls, E. T., Lind, H., Lind, W., & Ledingham, J. G. (1980) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1980.239.5.r476 · Cited by 228 · see citing works
Dieting and Depression Reexamined
Stunkard, A. J., & RUSH, J. (1974) · Annals of Internal Medicine · doi:10.7326/0003-4819-81-4-526 · Cited by 186 · see citing works
The Biology of Human Starvation, Vols. 1 & 2
Keys, A. B., Brozek, J. M., Henschel, A. F., Mickelsen, O., & TAYLOR, H. L. (1950) · Cited by 154 · see citing works
Brain stimulation and motivation : research and commentary.
Valenstein, E. S. (1973) · Medical Entomology and Zoology · Cited by 58 · see citing works
Dieting and depression: A methodological study.
Wadden, T. A., Stunkard, A. J., & Smoller, J. W. (1986) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.54.6.869 · Cited by 54 · see citing works
Yiin, Y.-M., Ackroff, K., & Sclafani, A. J. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.11.008 · Cited by 51 · see citing works
Investigations on the physiological controls of water and saline intake in C57BL/6 mice
Johnson, R. F., Beltz, T. G., Thunhorst, R. L., & Johnson, A. K. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00130.2003 · Cited by 51 · see citing works
Dieting and depression: A methodological study.
Wadden, T. A., Stunkard, A. J., & Smoller, J. W. (1986) · Journal of Consulting and Clinical Psychology · doi:10.1037//0022-006x.54.6.869 · Cited by 7 · see citing works
Cravens, R. W., & Renner, K. E. (1969) · Journal of Experimental Psychology · doi:10.1037/h0027777 · Cited by 6 · see citing works
Flagged first, then by citations
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Sorted by citations
Roth, B. L. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.040 · Cited by 1,742 · see citing works
Yang, Y., Chen, H., Heidari, A. A., & Gandomi, A. H. (2021) · Expert Systems with Applications · doi:10.1016/j.eswa.2021.114864 · Cited by 1,073 · see citing works
A Neural Circuit for Gut-Induced Reward
Han, W., Téllez, L. A., Perkins, M. H., Pérez-Martínez, I. O., Qu, T., Ferreira, J. G. P., Ferreira, T. L., Quinn, D., Liu, Z.-W., Gao, X., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.049 · Cited by 739 · see citing works
Obesity Pathogenesis: An Endocrine Society Scientific Statement
Schwartz, M. W., Seeley, R. J., Zeltser, L. M., Drewnowski, A., Ravussin, E., Redman, L. M., & Leibel, R. L. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00111 · Cited by 727 · see citing works
Leptin and the endocrine control of energy balance
Friedman, J. M. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0095-y · Cited by 661 · see citing works
Genetically encoded indicators of neuronal activity
Lin, M. Z., & Schnitzer, M. J. (2016) · Nature Neuroscience · doi:10.1038/nn.4359 · Cited by 631 · see citing works
Toward a Wiring Diagram Understanding of Appetite Control
Andermann, M. L., & Lowell, B. B. (2017) · Neuron · doi:10.1016/j.neuron.2017.06.014 · Cited by 608 · see citing works
Blaming the brain for obesity: integration of hedonic and homeostatic mechanisms
Berthoud, H.-R., Münzberg, H., & Morrison, C. D. (2017) · Gastroenterology · doi:10.1053/j.gastro.2016.12.050 · Cited by 445 · see citing works
Neuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding
Waterson, M. J., & Horváth, T. L. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.026 · Cited by 439 · see citing works
Thirst-associated preoptic neurons encode an aversive motivational drive.
Allen, W. E., DeNardo, L. A., Chen, M. Z., Liu, C. D., Loh, K. M., Fenno, L. E., Ramakrishnan, C., Deisseroth, K., & Luo, L. (2017) · Science · doi:10.1126/science.aan6747 · Cited by 390 · see citing works
Leeners, B., Geary, N., Tobler, P. N., & Asarian, L. (2017) · Human Reproduction Update · doi:10.1093/humupd/dmw045 · Cited by 407 · see citing works
Nieh, E. H., Vander Weele, C. M., Matthews, G. A., Presbrey, K. N., Wichmann, R., Leppla, C. A., Izadmehr, E. M., & Tye, K. M. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.035 · Cited by 387 · see citing works
Overlapping Brain Circuits for Homeostatic and Hedonic Feeding
Rossi, M. A., & Stuber, G. D. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.09.021 · Cited by 415 · see citing works
Thirst regulates motivated behavior through modulation of brainwide neural population dynamics
Allen, W. E., Chen, M. Z., Pichamoorthy, N., Tien, R. H., Pachitariu, M., Luo, L., & Deisseroth, K. A. (2019) · Science · doi:10.1126/science.aav3932 · Cited by 362 · see citing works
Melanocortin-4 receptor–regulated energy homeostasis
Krashes, M. J., Lowell, B. B., & Garfield, A. S. (2016) · Nature Neuroscience · doi:10.1038/nn.4202 · Cited by 358 · see citing works
“Liking” and “wanting” in eating and food reward: Brain mechanisms and clinical implications
Morales, I., & Berridge, K. C. (2020) · Physiology & Behavior · doi:10.1016/j.physbeh.2020.113152 · Cited by 346 · see citing works
Neural ensemble dynamics underlying a long-term associative memory
Grewe, B. F., Gründemann, J., Kitch, L. J., Lecoq, J. A., Parker, J. G., Marshall, J. D., Larkin, M. C., Jercog, P. E., Grenier, F., Li, J. Z., et al. (2017) · Nature · doi:10.1038/nature21682 · Cited by 351 · see citing works
Three Pillars for the Neural Control of Appetite
Sternson, S. M., & Eiselt, A.-K. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-104948 · Cited by 336 · see citing works
Self-citationResendez, S. L., Jennings, J. H., Ung, R. L., Namboodiri, V. M. K., Zhou, Z. C., Otis, J. M., Nomura, H., McHenry, J. A., Kosyk, O., & Stuber, G. D. (2016) · Nature Protocols · doi:10.1038/nprot.2016.021 · Cited by 331 · see citing works
Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism
García‐Cáceres, C., Balland, É., Prévot, V., Luquet, S. H., Woods, S. C., Koch, M., Horváth, T. L., Yi, C., Chowen, J. A., Verkhratsky, A., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0286-y · Cited by 326 · see citing works
The Homeostatic Force of Ghrelin.
Yanagi, S., Sato, T., Kangawa, K., & Nakazato, M. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.008 · Cited by 293 · see citing works
Homeostatic circuits selectively gate food cue responses in insular cortex
Livneh, Y., Ramesh, R. N., Burgess, C. R., Levandowski, K. M., Madara, J. C., Fenselau, H., Goldey, G. J., Diaz, V. E., Jikomes, N., Resch, J. M., et al. (2017) · Nature · doi:10.1038/nature22375 · Cited by 316 · see citing works
Encoding of danger by parabrachial CGRP neurons
Campos, C., Bowen, A. J., Roman, C. W., & Palmiter, R. D. (2018) · Nature · doi:10.1038/nature25511 · Cited by 307 · see citing works
Hunger-Driven Motivational State Competition
Burnett, C. J., Li, C., Webber, E., Tsaousidou, E., Xue, S. Y., Brüning, J. C., & Krashes, M. J. (2016) · Neuron · doi:10.1016/j.neuron.2016.08.032 · Cited by 305 · see citing works
Mandelblat-Cerf, Y., Ramesh, R. N., Burgess, C. R., Patella, P., Yang, Z., Lowell, B. B., & Andermann, M. L. (2015) · eLife · doi:10.7554/elife.07122 · Cited by 290 · see citing works
Thirst neurons anticipate the homeostatic consequences of eating and drinking
Zimmerman, C. A., Lin, Y.-C., Leib, D. E., Guo, L., Huey, E. L., Daly, G. E., Chen, Y., & Knight, Z. A. (2016) · Nature · doi:10.1038/nature18950 · Cited by 283 · see citing works
Agouti-related peptide neural circuits mediate adaptive behaviors in the starved state
Padilla, S. L., Qiu, J., Soden, M. E., Sanz, E., Nestor, C. C., Barker, F. D., Quintana, A., Zweifel, L. S., Rønnekleiv, O. K., Kelly, M. J., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4274 · Cited by 293 · see citing works
Dynamics of Gut-Brain Communication Underlying Hunger
Beutler, L. R., Chen, Y., Ahn, J. S., Lin, Y.-C., Essner, R. A., & Knight, Z. A. (2017) · Neuron · doi:10.1016/j.neuron.2017.09.043 · Cited by 286 · see citing works
Neural mechanisms of social homeostasis
Matthews, G. A., & Tye, K. M. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14016 · Cited by 273 · see citing works
Arcuate Nucleus-Dependent Regulation of Metabolism—Pathways to Obesity and Diabetes Mellitus
Jaïs, A., & Brüning, J. C. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab025 · Cited by 282 · see citing works
Evolving Concepts of Emotion and Motivation
Berridge, K. C. (2018) · Frontiers in Psychology · doi:10.3389/fpsyg.2018.01647 · Cited by 273 · see citing works
AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue
Steculorum, S. M., Ruud, J., Karakasilioti, I., Backes, H., Engström, L., Timper, K., Hess, M. E., Tsaousidou, E., Mauer, J., Vogt, M. C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.02.044 · Cited by 279 · see citing works
Allostasis: A brain-centered, predictive mode of physiological regulation
Schulkin, J., & Sterling, P. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.07.010 · Cited by 265 · see citing works
The melanocortin pathway and control of appetite-progress and therapeutic implications
Baldini, G., & Phelan, K. D. (2019) · Journal of Endocrinology · doi:10.1530/joe-18-0596 · Cited by 279 · see citing works
Parabrachial CGRP Neurons Control Meal Termination
Campos, C. A., Bowen, A. J., Schwartz, M. W., & Palmiter, R. D. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.006 · Cited by 262 · see citing works
Neural circuits underlying thirst and fluid homeostasis
Zimmerman, C. A., Leib, D. E., & Knight, Z. A. (2017) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.71 · Cited by 262 · see citing works
Central amygdala circuits modulate food consumption through a positive-valence mechanism
Douglass, A. M., Kucukdereli, H., Ponserre, M., Marković, M., Gründemann, J., Strobel, C., Morales, P. L. A., Conzelmann, K., Lüthi, A., & Klein, R. (2017) · Nature Neuroscience · doi:10.1038/nn.4623 · Cited by 257 · see citing works
Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss
Henry, F. E., Sugino, K., Tozer, A., Branco, T., & Sternson, S. M. (2015) · eLife · doi:10.7554/elife.09800 · Cited by 242 · see citing works
Self-citationThe melanocortin pathway and energy homeostasis: From discovery to obesity therapy
Yeo, G. S. H., Chao, D. H. M., Siegert, A., Koerperich, Z. M., Ericson, M. D., Simonds, S. E., Larson, C. M., Luquet, S. H., Clarke, I. J., Sharma, S. D., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101206 · Cited by 242 · see citing works
Estimation of Current and Future Physiological States in Insular Cortex
Livneh, Y., Sugden, A. U., Madara, J. C., Essner, R. A., Flores, V. I., Sugden, L. A., Resch, J. M., Lowell, B. B., & Andermann, M. L. (2020) · Neuron · doi:10.1016/j.neuron.2019.12.027 · Cited by 209 · see citing works
The emergence and influence of internal states
Flavell, S. W., Gogolla, N., Lovett-Barron, M., & Zelikowsky, M. (2022) · Neuron · doi:10.1016/j.neuron.2022.04.030 · Cited by 233 · see citing works
Dynamic GABAergic afferent modulation of AgRP neurons
Garfield, A. S., Shah, B. P., Burgess, C. R., Li, M. M., Li, C., Steger, J. S., Madara, J. C., Campbell, J. N., Kroeger, D., Scammell, T. E., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4392 · Cited by 211 · see citing works
Amygdala ensembles encode behavioral states
Gründemann, J., Bitterman, Y., Lu, T., Krabbe, S., Grewe, B. F., Schnitzer, M. J., & Lüthi, A. (2019) · Science · doi:10.1126/science.aav8736 · Cited by 223 · see citing works
A Neural Circuit for the Suppression of Pain by a Competing Need State
Alhadeff, A. L., Su, Z., Hernandez, E., Klima, M. L., Phillips, S. Z., Holland, R. A., Guo, C., Hantman, A. W., De Jonghe, B. C., & Betley, J. N. (2018) · Cell · doi:10.1016/j.cell.2018.02.057 · Cited by 218 · see citing works
Self-citationOLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin
Li, E., Shan, H., Chen, L., Long, A., Zhang, Y., Liu, Y., Jia, L., Wei, F., Han, J., Li, T., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.05.022 · Cited by 221 · see citing works
Integrative neurocircuits that control metabolism and food intake
Brüning, J. C., & Fenselau, H. (2023) · Science · doi:10.1126/science.abl7398 · Cited by 214 · see citing works
Nutritive, Post-ingestive Signals Are the Primary Regulators of AgRP Neuron Activity
Su, Z., Alhadeff, A. L., & Betley, J. N. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.036 · Cited by 216 · see citing works
Self-citationHomeostasis Meets Motivation in the Battle to Control Food Intake
Ferrario, C. R., Labouèbe, G., Liu, S., Nieh, E. H., Routh, V. H., Xu, S., & O’Connor, E. C. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2338-16.2016 · Cited by 213 · see citing works
Self-citationHypothalamic Circuits for Predation and Evasion
Li, Y., Zeng, J., Zhang, J.-E., Yue, C., Zhong, W., Liu, Z., Feng, Q., & Luo, M. (2018) · Neuron · doi:10.1016/j.neuron.2018.01.005 · Cited by 212 · see citing works
Li, M. M., Madara, J. C., Steger, J. S., Krashes, M. J., Balthasar, N., Campbell, J. N., Resch, J. M., Conley, N. J., Garfield, A. S., & Lowell, B. B. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.028 · Cited by 195 · see citing works
Hunger neurons drive feeding through a sustained, positive reinforcement signal.
Chen, Y., Lin, Y.-C., Zimmerman, C. A., Essner, R. A., & Knight, Z. A. (2016) · eLife · doi:10.7554/elife.18640 · Cited by 196 · see citing works
The timing of action determines reward prediction signals in identified midbrain dopamine neurons
Coddington, L. T., & Dudman, J. T. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0245-7 · Cited by 206 · see citing works
Behavioral state coding by molecularly defined paraventricular hypothalamic cell type ensembles
Xu, S., Yang, H., Menon, V., Lemire, A. L., Wang, L., Henry, F. E., Turaga, S. C., & Sternson, S. M. (2020) · Science · doi:10.1126/science.abb2494 · Cited by 197 · see citing works
Self-citationDREADD Agonist 21 Is an Effective Agonist for Muscarinic-Based DREADDs in Vitro and in Vivo
Thompson, K. J., Khajehali, E., Bradley, S. J., Navarrete, J. S., Huang, X., Slocum, S. T., Jin, J. J., Liu, J., Xiong, Y., Olsen, R. H. J., et al. (2018) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.8b00012 · Cited by 195 · see citing works
The Sense of Smell Impacts Metabolic Health and Obesity
Riera, C. E., Tsaousidou, E., Halloran, J., Follett, P., Hahn, O., Pereira, M. M. A., Ruud, L. E., Alber, J., Tharp, K., Anderson, C. M., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.015 · Cited by 191 · see citing works
POMC neuronal heterogeneity in energy balance and beyond: an integrated view
Quarta, C., Claret, M., Zeltser, L. M., Williams, K. W., Yeo, G. S. H., Tschöp, M. H., Diano, S., Brüning, J. C., & Cota, D. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00345-3 · Cited by 189 · see citing works
High-fat food biases hypothalamic and mesolimbic expression of consummatory drives
Mazzone, C. M., Liang-Guallpa, J., Li, C., Wolcott, N. S., Boone, M. H., Southern, M., Kobzar, N. P., Salgado, I. D. A., Reddy, D., Sun, F., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0684-9 · Cited by 187 · see citing works
Zhao, Z., Chen, Z., Xiang, X., Hu, M., Xie, H., Jia, X., Cai, F., Cui, Y., Chen, Z., Qian, L., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0404-5 · Cited by 184 · see citing works
Hypothalamic detection of macronutrients via multiple gut-brain pathways
Goldstein, N., McKnight, A. D., Carty, J. R. E., Arnold, M., Betley, J. N., & Alhadeff, A. L. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2020.12.018 · Cited by 183 · see citing works
Self-citationA common neuroendocrine substrate for diverse general anesthetics and sleep
Jiang-Xie, L.-F., Yin, L., Zhao, S., Prevosto, V., Han, B.-X., Dzirasa, K., & Wang, F. (2019) · Neuron · doi:10.1016/j.neuron.2019.03.033 · Cited by 173 · see citing works
Hierarchical neural architecture underlying thirst regulation
Augustine, V., Gökçe, S. K., Lee, S., Wang, B., Davidson, T. J., Reimann, F. M., Gribble, F. M., Deisseroth, K. A., Lois, C., & Oka, Y. (2018) · Nature · doi:10.1038/nature25488 · Cited by 169 · see citing works
A Taste Circuit that Regulates Ingestion by Integrating Food and Hunger Signals
Yapici, N., Cohn, R., Schusterreiter, C., Ruta, V., & Vosshall, L. B. (2016) · Cell · doi:10.1016/j.cell.2016.02.061 · Cited by 162 · see citing works
The physiological control of eating: signals, neurons, and networks
Watts, A. G., Kanoski, S. E., Sanchez-Watts, G., & Langhans, W. (2022) · Physiological Reviews · doi:10.1152/physrev.00028.2020 · Cited by 168 · see citing works
Adaptive disinhibitory gating by VIP interneurons permits associative learning
Krabbe, S., Paradiso, E., d‘Aquin, S., Bitterman, Y., Courtin, J., Xu, C., Yonehara, K., Marković, M., Müller, C. R., Eichlisberger, T., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0508-y · Cited by 161 · see citing works
A Vagal-NTS Neural Pathway that Stimulates Feeding
Chen, J. W., Cheng, M., Wang, L. Y., Zhang, L., Xu, D., Cao, P., Wang, F., Herzog, H., Song, S., & Zhan, C. (2020) · Current Biology · doi:10.1016/j.cub.2020.07.084 · Cited by 167 · see citing works
Regulation of starvation-induced hyperactivity by insulin and glucagon signaling in adult Drosophila
Yu, Y., Huang, R., Ye, J., Zhang, V., Wu, C., Cheng, G., Jia, J., & Wang, L. (2016) · eLife · doi:10.7554/elife.15693 · Cited by 167 · see citing works
Self-citationFast and accurate sCMOS noise correction for fluorescence microscopy
Mandracchia, B., Hua, X., Guo, C., Son, J., Urner, T. M., & Jia, S. (2020) · Nature Communications · doi:10.1038/s41467-019-13841-8 · Cited by 162 · see citing works
An appetite for life: brain regulation of hunger and satiety
Heisler, L. K., & Lam, D. D. (2017) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2017.09.002 · Cited by 160 · see citing works
AgRP neurons: Regulators of feeding, energy expenditure, and behavior
Deem, J. D., Faber, C. L., & Morton, G. J. (2021) · FEBS Journal · doi:10.1111/febs.16176 · Cited by 158 · see citing works
Alcantara, I. C., Tapia, A. P. M., Aponte, Y., & Krashes, M. J. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00611-y · Cited by 155 · see citing works
NTS Catecholamine Neurons Mediate Hypoglycemic Hunger via Medial Hypothalamic Feeding Pathways
Aklan, İ., Sayar, N., Yavuz, Y., Ateş, T., Çoban, İ., Alkan, F. K., Filiz, G., Topcu, I. C., Öncül, M., Dilsiz, P., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.016 · Cited by 152 · see citing works
MIN1PIPE: A Miniscope 1-Photon-Based Calcium Imaging Signal Extraction Pipeline
Lu, J., Li, C., Alvarado, J. S., Zhou, Z., Frӧhlich, F., MOONEY, R. D., & Wang, F. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.05.062 · Cited by 155 · see citing works
Rapid, biphasic CRF neuronal responses encode positive and negative valence
Kim, J., Lee, S., Fang, Y., Shin, A., Park, S., Hashikawa, K., Bhat, S., Kim, D., Sohn, J., Lin, D., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0342-2 · Cited by 152 · see citing works
Neural Control and Modulation of Thirst, Sodium Appetite, and Hunger
Augustine, V., Lee, S., & Oka, Y. (2020) · Cell · doi:10.1016/j.cell.2019.11.040 · Cited by 135 · see citing works
Reward Inhibits Paraventricular CRH Neurons to Relieve Stress
Yuan, Y., Wu, W., Chen, M., Cai, F., Fan, C., Shen, W., Sun, W., & Hu, J. (2019) · Current Biology · doi:10.1016/j.cub.2019.02.048 · Cited by 151 · see citing works
An excitatory ventral hippocampus to lateral septum circuit that suppresses feeding
Sweeney, P., & Yang, Y. (2015) · Nature Communications · doi:10.1038/ncomms10188 · Cited by 147 · see citing works
60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH
Anderson, E. J. P., Çakır, I., Carrington, S. J. S., Cone, R. D., Ghamari‐Langroudi, M., Gillyard, T. R., Gimenez, L. E., & Litt, M. J. (2016) · Journal of Molecular Endocrinology · doi:10.1530/jme-16-0014 · Cited by 149 · see citing works
Li, C., Navarrete, J. S., Liang-Guallpa, J., Lü, C., Funderburk, S. C., Chang, R. B., Liberles, S. D., Olson, D. P., & Krashes, M. J. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.10.016 · Cited by 145 · see citing works
Ventromedial Hypothalamus and the Generation of Aggression
Hashikawa, Y., Hashikawa, K., Falkner, A. L., & Lin, D. (2017) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2017.00094 · Cited by 141 · see citing works
Reverse-translational identification of a cerebellar satiation network
Low, A. Y. T., Goldstein, N., Gaunt, J. R., Huang, K.-P., Zainolabidin, N., Yip, A. K. K., Carty, J. R. E., Choi, J. Y., Miller, A. M., Ho, H. S. T., et al. (2021) · Nature · doi:10.1038/s41586-021-04143-5 · Cited by 135 · see citing works
Self-citationNeural control of parental behaviors
Kohl, J., & Dulac, C. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.02.002 · Cited by 136 · see citing works
Alhadeff, A. L., Goldstein, N., Park, O., Klima, M. L., Vargas, A. P.-D., & Betley, J. N. (2019) · Neuron · doi:10.1016/j.neuron.2019.05.050 · Cited by 138 · see citing works
Self-citationChemogenetic Tools for Causal Cellular and Neuronal Biology
Atasoy, D., & Sternson, S. M. (2017) · Physiological Reviews · doi:10.1152/physrev.00009.2017 · Cited by 130 · see citing works
Self-citationImaging large-scale cellular activity in spinal cord of freely behaving mice
Sekiguchi, K. J., Shekhtmeyster, P., Merten, K., Arena, A., Cook, D., Hoffman, E. A., Ngo, A., & Nimmerjahn, A. (2016) · Nature Communications · doi:10.1038/ncomms11450 · Cited by 134 · see citing works
Calcium imaging of sleep-wake related neuronal activity in the dorsal pons
Cox, J., Pinto, L., & Dan, Y. (2016) · Nature Communications · doi:10.1038/ncomms10763 · Cited by 133 · see citing works
Optogenetics: 10 years after ChR2 in neurons—views from the community
Adamantidis, A., Arber, S., Bains, J. S., Bamberg, E., Bonci, A., Buzsáki, G., Cardin, J. A., Costa, R. M., Dan, Y., Goda, Y., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4106 · Cited by 130 · see citing works
Self-citationXia, G., Han, Y., Meng, F., He, Y., Srisai, D., Farías, M., Dang, M., Palmiter, R. D., Xu, Y., & Wu, Q. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01053-w · Cited by 133 · see citing works
The neurobiology of parenting: A neural circuit perspective
Kohl, J., Autry, A. E., & Dulac, C. G. (2016) · BioEssays · doi:10.1002/bies.201600159 · Cited by 131 · see citing works
Homeostatic and non-homeostatic controls of feeding behavior: Distinct vs. common neural systems
Liu, C. M., & Kanoski, S. E. (2018) · Physiology & Behavior · doi:10.1016/j.physbeh.2018.02.011 · Cited by 131 · see citing works
PNOCARC Neurons Promote Hyperphagia and Obesity upon High-Fat-Diet Feeding
Jais, A., Paeger, L., Sotelo-Hitschfeld, T., Bremser, S., Prinzensteiner, M., Klemm, P., Mykytiuk, V., Widdershooven, P. J. M., Vesting, A. J., Grzelka, K., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.03.022 · Cited by 129 · see citing works
Food Perception Primes Hepatic ER Homeostasis via Melanocortin-Dependent Control of mTOR Activation
Brandt, C., Nolte, H., Henschke, S., Engström, L., Awazawa, M., Morgan, D. A., Gabel, P., Sprenger, H., Hess, M. E., Günther, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.015 · Cited by 130 · see citing works
Essner, R. A., Smith, A. G., Jamnik, A. A., Ryba, A. R., Trutner, Z. D., & Carter, M. E. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.0798-17.2017 · Cited by 128 · see citing works
The Forebrain Thirst Circuit Drives Drinking through Negative Reinforcement
Leib, D. E., Zimmerman, C. A., Poormoghaddam, A., Huey, E. L., Ahn, J. S., Lin, Y.-C., Tan, C. L., Chen, Y., & Knight, Z. A. (2017) · Neuron · doi:10.1016/j.neuron.2017.11.041 · Cited by 128 · see citing works
A gut-to-brain signal of fluid osmolarity controls thirst satiation
Zimmerman, C. A., Huey, E. L., Ahn, J. S., Beutler, L. R., Tan, C. L., Kosar, S., Bai, L., Chen, Y., Corpuz, T. V., Madisen, L., et al. (2019) · Nature · doi:10.1038/s41586-019-1066-x · Cited by 128 · see citing works
Sustained NPY signaling enables AgRP neurons to drive feeding
Chen, Y., Essner, R. A., Kosar, S., Miller, O. H., Lin, Y.-C., Mesgarzadeh, S., & Knight, Z. A. (2019) · eLife · doi:10.7554/elife.46348 · Cited by 128 · see citing works
The Neural Basis of Escape Behavior in Vertebrates
Branco, T., & Redgrave, P. (2020) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-100219-122527 · Cited by 129 · see citing works
The cellular mechanism for water detection in the mammalian taste system
Zocchi, D., Wennemuth, G., & Oka, Y. (2017) · Nature Neuroscience · doi:10.1038/nn.4575 · Cited by 127 · see citing works
Vagal sensory neurons and gut-brain signaling
Yu, C. D., Xu, Q. J., & Chang, R. B. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.03.006 · Cited by 125 · see citing works
Gotthardt, J. D., Verpeut, J. L., Yeomans, B. L., Yang, J., Yasrebi, A., Roepke, T. A., & Bello, N. T. (2015) · Endocrinology · doi:10.1210/en.2015-1622 · Cited by 123 · see citing works
An open source, wireless capable miniature microscope system
Liberti, W. A., Perkins, L. N., Leman, D. P., & Gardner, T. J. (2017) · Journal of Neural Engineering · doi:10.1088/1741-2552/aa6806 · Cited by 123 · see citing works
- Authors
- Betley, J. N., Xu, S., Cao, Z. F. H., Gong, R., Magnus, C. J., Yu, Y., & Sternson, S. M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Sternson, Scott M.
- ORCID
- Venue
- Nature
- Published
- 2015-04-27
- Volume
- 521
- Issue
- 7551
- Pages
- 180-185
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4567040
- OpenAlex
- W2101995469
- Cited by
- 704
- References
- 49
- Citations by year
- 2026: 32 · 2025: 73 · 2024: 70 · 2023: 68 · 2022: 50 · 2021: 72 · 2020: 65 · 2019: 73 · 2018: 64 · 2017: 62 · 2016: 54 · 2015: 21
- FWCI
- 37.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- hunger, thirst, homeostasis, AgRP neurons, subfornical organ, negative valence, teaching signal, motivation in learning, avoidance conditioning, energy homeostasis, fluid homeostasis
- MeSH terms
- Animals, Cues, Dehydration, Drinking, Eating, Food, Food Preferences, Homeostasis, Hunger, Hypothalamus, Male, Neurons, Starvation, Thirst, Models, Animal, Mice, Agouti-Related Protein
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