Behavioral dissection of hunger states in Drosophila
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Abstract
Hunger is a motivational drive that promotes feeding, and it can be generated by the physiological need to consume nutrients as well as the hedonic properties of food. Brain circuits and mechanisms that regulate feeding have been described, but which of these contribute to the generation of motive forces that drive feeding is unclear. Here, we describe our first efforts at behaviorally and neuronally distinguishing hedonic from homeostatic hunger states in Drosophila melanogaster and propose that this system can be used as a model to dissect the molecular mechanisms that underlie feeding motivation. We visually identify and quantify behaviors exhibited by hungry flies and find that increased feeding duration is a behavioral signature of hedonic feeding motivation. Using a genetically encoded marker of neuronal activity, we find that the mushroom body (MB) lobes are activated by hedonic food environments, and we use optogenetic inhibition to implicate a dopaminergic neuron cluster (protocerebral anterior medial [PAM]) to α’/β’ MB circuit in hedonic feeding motivation. The identification of discrete hunger states in flies and the development of behavioral assays to measure them offers a framework to begin dissecting the molecular and circuit mechanisms that generate motivational states in the brain.
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Further specific aminergic circuits will activate the mushroom body outputs when entering environments associated with feeding, but flies can only learn about food stimuli if they are hungry.
“Further specific aminergic circuits will activate the mushroom body outputs when entering environments associated with feeding [75], but flies can only learn about food stimuli if they are hungry [69].”
From Phenomenal interface theory: a model for basal consciousness (2025) · cites this paper as [75]
The ‘Identification of neural correlates of hedonic hunger’ section reports increased activity in mushroom body lobes in hedonic food environments and identifies a dopaminergic PAM-to-mushroom-body circuit required for hedonic feeding. It does not establish that the aminergic circuit activates mushroom body outputs specifically when flies enter those environments. The separate claim about learning only while hungry is attached to citation [69], not this source. (LLM, conf=0.84)
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Cites
Food reward: brain substrates of wanting and liking
Berridge, K. C. (1996) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(95)00033-b · Cited by 1,901 · 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
“Liking” and “wanting” food rewards: Brain substrates and roles in eating disorders
Berridge, K. C. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.02.044 · Cited by 1,147 · 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
Expression of ghrelin receptor mRNA in the rat and the mouse brain
Zigman, J. M., Jones, J. E., Lee, C. E., Saper, C. B., & Elmquist, J. K. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.20823 · Cited by 1,074 · see citing works
The neuronal architecture of the mushroom body provides a logic for associative learning
Aso, Y., Hattori, D., Yu, Y., Johnston, R. M., Iyer, N. A., Ngo, T.-T., Dionne, H., Abbott, L., Axel, R., Tanimoto, H., et al. (2014) · eLife · doi:10.7554/elife.04577 · Cited by 1,051 · see citing works
Hedonic hunger: A new dimension of appetite?
Lowe, M. R., & Butryn, M. L. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.04.006 · Cited by 739 · see citing works
Neurons for hunger and thirst transmit a negative-valence teaching signal
Betley, J. N., Xu, S., Cao, Z. F. H., Gong, R., Magnus, C. J., Yu, Y., & Sternson, S. M. (2015) · Nature · doi:10.1038/nature14416 · Cited by 704 · see citing works
A subset of dopamine neurons signals reward for odour memory in Drosophila
Liu, C., Plaçais, P.-Y., Yamagata, N., Pfeiffer, B. D., Aso, Y., Friedrich, A. B., Siwanowicz, I., Rubin, G. M., Préat, T., & Tanimoto, H. (2012) · Nature · doi:10.1038/nature11304 · Cited by 623 · see citing works
Layered reward signalling through octopamine and dopamine in Drosophila
Burke, C. J., Huetteroth, W., Owald, D., Perisse, E., Krashes, M. J., Das, G., Gohl, D., Silies, M., Certel, S., & Waddell, S. (2012) · Nature · doi:10.1038/nature11614 · Cited by 614 · 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 606 · see citing works
Willesen, M. G., Kristensen, P., & Rømer, J. (1999) · Neuroendocrinology · doi:10.1159/000054491 · Cited by 605 · see citing works
Mao, Z. (2009) · Frontiers in Neural Circuits · doi:10.3389/neuro.04.005.2009 · Cited by 532 · see citing works
Neuronal assemblies of the <i>Drosophila</i> mushroom body
Tanaka, N. K., Tanimoto, H., & Ito, K. (2008) · Journal of Comparative Neurology · doi:10.1002/cne.21692 · Cited by 470 · see citing works
Labeling of active neural circuits in vivo with designed calcium integrators
Fosque, B. F., Sun, Y., Dana, H., Yang, C.-T., Ohyama, T., Tadross, M. R., Patel, R. H., Zlatic, M., Kim, D. S., Ahrens, M. B., et al. (2015) · Science · doi:10.1126/science.1260922 · Cited by 458 · see citing works
Tripartite Mushroom Body Architecture Revealed by Antigenic MarkersPreprint
Crittenden, J. R., Skoulakis, E. M. C., Han, K., Kalderon, D., & Davis, R. L. (1998) · Learning & Memory · doi:10.1101/lm.5.1.38 · Cited by 446 · see citing works
Hedonic Hot Spots in the Brain
Peciña, S., Smith, K. S., & Berridge, K. C. (2006) · The Neuroscientist · doi:10.1177/1073858406293154 · Cited by 441 · 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
Fighting fruit flies: A model system for the study of aggression
Chen, S., Lee, A. Y., Bowens, N. M., Huber, R., & Kravitz, E. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082102599 · Cited by 412 · see citing works
The Mushroom Body of Adult Drosophila Characterized by GAL4 Drivers
Aso, Y., Grübel, K., Busch, S., Friedrich, A. B., Siwanowicz, I., & Tanimoto, H. (2009) · Journal of Neurogenetics · doi:10.1080/01677060802471718 · Cited by 381 · see citing works
A protocol for dissecting Drosophila melanogaster brains for live imaging or immunostaining
Wu, J., & Luo, L. (2006) · Nature Protocols · doi:10.1038/nprot.2006.336 · Cited by 368 · see citing works
Subdivision of the drosophila mushroom bodies by enhancer-trap expression patterns
Yang, M., Armstrong, J. D., Vilinsky, I., Strausfeld, N. J., & Kaiser, K. (1995) · Neuron · doi:10.1016/0896-6273(95)90063-2 · Cited by 348 · see citing works
Quantifying Behavior the Jwatcher Way
Blumstein, D. T., & Daniel, J. C. (2007) · Cited by 343 · 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
Optogenetic inhibition of behavior with anion channelrhodopsins
Mohammad, F., Stewart, J. C., Ott, S., Chlebikova, K., Chua, J. Y., Koh, T.-W., Ho, J., & Claridge-Chang, A. (2017) · Nature Methods · doi:10.1038/nmeth.4148 · Cited by 276 · see citing works
Sweet Taste and Nutrient Value Subdivide Rewarding Dopaminergic Neurons in Drosophila
Huetteroth, W., Perisse, E., Lin, S., Klappenbach, M., Burke, C., & Waddell, S. (2015) · Current Biology · doi:10.1016/j.cub.2015.01.036 · Cited by 265 · see citing works
Testing Protein Leverage in Lean Humans: A Randomised Controlled Experimental Study
Gosby, A. K., Conigrave, A. D., Lau, N. S., Iglesias, M. A., Hall, R. M., Jebb, S. A., Brand-Miller, J. C., Caterson, I. D., Raubenheimer, D., & Simpson, S. J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025929 · Cited by 254 · see citing works
Automated monitoring and quantitative analysis of feeding behaviour in Drosophila
Itskov, P. M., Moreira, J.-M., Vinnik, E., Lopes, G., Safarik, S., Dickinson, M. H., & Ribeiro, C. (2014) · Nature Communications · doi:10.1038/ncomms5560 · Cited by 239 · see citing works
Quantifying Drosophila food intake: comparative analysis of current methodology
Deshpande, S. A., Carvalho, G. B., Amador, A., Phillips, A. M., Hoxha, S., Lizotte, K. J., & Ja, W. W. (2014) · Nature Methods · doi:10.1038/nmeth.2899 · Cited by 237 · 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 234 · see citing works
Remembering Nutrient Quality of Sugar in Drosophila
Burke, C. J., & Waddell, S. (2011) · Current Biology · doi:10.1016/j.cub.2011.03.032 · Cited by 221 · see citing works
Tsao, C.-H., Chen, C.-C., Lin, C.-H., Yang, H.-Y., & Lin, S. (2018) · eLife · doi:10.7554/elife.35264 · Cited by 214 · see citing works
Geometric analysis of macronutrient intake in humans: the power of protein?
Simpson, S. J., Batley, R., & Raubenheimer, D. (2003) · Appetite · doi:10.1016/s0195-6663(03)00049-7 · Cited by 210 · see citing works
FLIC: High-Throughput, Continuous Analysis of Feeding Behaviors in Drosophila
Ro, J., Harvanek, Z. M., & Pletcher, S. D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0101107 · Cited by 189 · see citing works
Self-citationA single pair of neurons links sleep to memory consolidation in Drosophila melanogaster
Haynes, P. R., Christmann, B. L., & Griffith, L. C. (2015) · eLife · doi:10.7554/elife.03868 · Cited by 186 · see citing works
Palatability Can Drive Feeding Independent of AgRP Neurons
Denis, R. G. P., Joly-Amado, A., Webber, E., Langlet, F., Schaeffer, M., Padilla, S. L., Cansell, C., Dehouck, B., Castel, J., Delbès, A.-S., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.011 · Cited by 164 · see citing works
Fulton, S. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.10.003 · 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
Casarrubea, M., Jonsson, G. K., Faulisi, F., Sorbera, F., Giovanni, G. D., Benigno, A., Crescimanno, G., & Magnússon, M. S. (2014) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2014.09.024 · Cited by 145 · see citing works
High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster
May, C. E., Vaziri, A., Qi, L. Y., Grushko, O., Khabiri, M., Wang, Q., Holme, K. J., Pletcher, S. D., Freddolino, L., Neely, G. G., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.027 · Cited by 135 · see citing works
Self-citationBranch-specific plasticity of a bifunctional dopamine circuit encodes protein hunger
Liu, Q., Tabuchi, M., Liu, S., Kodama, L., Horiuchi, W., Daniels, J., Chiu, L. T., Baldoni, D., & Wu, M. N. (2017) · Science · doi:10.1126/science.aal3245 · Cited by 128 · see citing works
Food wanting is mediated by transient activation of dopaminergic signaling in the honey bee brain
Huang, J., Zhang, Z., Feng, W., Zhao, Y., Aldanondo, A., Sanchez, M. G. D. B., Paoli, M., Rolland, A., Li, Z., Nie, H., et al. (2022) · Science · doi:10.1126/science.abn9920 · Cited by 124 · see citing works
Measurement of solid food intake in Drosophila via consumption-excretion of a dye tracer
Shell, B. C., Schmitt, R. E., Lee, K. M., Johnson, J. C., Chung, B. Y., Pletcher, S. D., & Grotewiel, M. (2018) · Scientific Reports · doi:10.1038/s41598-018-29813-9 · Cited by 117 · see citing works
Self-citationXu, Y., Lu, Y., Cassidy, R. M., Mangieri, L. R., Zhu, C., Xugen, H., Jiang, Z., Justice, N. J., Xu, Y., Arenkiel, B. R., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11399-z · Cited by 96 · see citing works
Behavior of Hector's Dolphin: Classifying Behavior by Sequence Analysis
Slooten, E. (1994) · Journal of Mammalogy · doi:10.2307/1382477 · Cited by 86 · see citing works
Ghiglieri, O., Gambarana, C., Scheggi, S., Tagliamonte, A., Willner, P., & Montis, M. G. D. (1997) · Behavioural Pharmacology · doi:10.1097/00008877-199711000-00018 · Cited by 78 · see citing works
Satiation state-dependent dopaminergic control of foraging in Drosophila
Landayan, D., Feldman, D. S., & Wolf, F. W. (2018) · Scientific Reports · doi:10.1038/s41598-018-24217-1 · Cited by 77 · see citing works
Dietary sugar inhibits satiation by decreasing the central processing of sweet taste
May, C. E., Rosander, J., Gottfried, J., Dennis, E., & Dus, M. (2020) · eLife · doi:10.7554/elife.54530 · Cited by 72 · see citing works
THE UTILIZATION OF SUGARS AND OTHER SUBSTANCES BY DROSOPHILA
Hassett, C. C. (1948) · Biological Bulletin · doi:10.2307/1538158 · Cited by 71 · see citing works
Serotonin signaling mediates protein valuation and aging
Ro, J., Pak, G., Malec, P. A., Lyu, Y., Allison, D. B., Kennedy, R. T., & Pletcher, S. D. (2016) · eLife · doi:10.7554/elife.16843 · Cited by 67 · see citing works
Self-citationHypothalamic control of interoceptive hunger
Siemian, J. N., Arenivar, M. A., Sarsfield, S., & Aponte, Y. (2021) · Current Biology · doi:10.1016/j.cub.2021.06.048 · Cited by 65 · see citing works
A Brain Module for Scalable Control of Complex, Multi-motor Threat Displays
Duistermars, B. J., Pfeiffer, B. D., Hoopfer, E. D., & Anderson, D. J. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.027 · Cited by 63 · see citing works
Effects of hunger on neuronal histone modifications slow aging in Drosophila
Weaver, K. J., Holt, R. A., Henry, E., Lyu, Y., & Pletcher, S. D. (2023) · Science · doi:10.1126/science.ade1662 · Cited by 61 · see citing works
Self-citationArcego, D. M., Krolow, R., Lampert, C., Toniazzo, A. P., Garcia, E. D. S., Lazzaretti, C., Costa, G., Scorza, C., & Dalmaz, C. (2020) · Appetite · doi:10.1016/j.appet.2020.104739 · Cited by 54 · see citing works
Brain circuits for promoting homeostatic and non-homeostatic appetites
Ahn, B. H., Kim, M., & Kim, S. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00758-4 · Cited by 53 · see citing works
Remembering Components of Food in Drosophila
Das, G., Lin, S., & Waddell, S. (2016) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2016.00004 · Cited by 51 · see citing works
Behavioral signatures of structured feature detection during courtship in Drosophila
Ning, J., Li, Z., Zhang, X., Wang, J., Chen, D., Liu, Q., & Sun, Y. (2022) · Current Biology · doi:10.1016/j.cub.2022.01.024 · Cited by 39 · see citing works
Octopamine mediates sugar relief from a chronic-stress-induced depression-like state in Drosophila
Hermanns, T., Graf-Boxhorn, S., Poeck, B., & Strauß, R. (2022) · Current Biology · doi:10.1016/j.cub.2022.07.016 · Cited by 37 · see citing works
Combining Quantitative and Qualitative Data in the Study of Feeding Behavior in Male Wistar Rats
Casarrubea, M., Aiello, S., Giovanni, G. D., Santangelo, A., Palacino, M., & Crescimanno, G. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.00881 · Cited by 36 · see citing works
Altherr, E. B., Rainwater, A., Kaviani, D., Tang, Q., & Güler, A. D. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113470 · Cited by 33 · see citing works
Shell, B. C., Luo, Y., Pletcher, S. D., & Grotewiel, M. (2021) · Scientific Reports · doi:10.1038/s41598-021-99483-7 · Cited by 29 · see citing works
Self-citationCannon, W. B., & Washburn, A. L. (1993) · Obesity Research · doi:10.1002/j.1550-8528.1993.tb00033.x · Cited by 26 · see citing works
Edwards, K. A., Hoppa, M. B., & Bosco, G. (2020) · Frontiers in Neural Circuits · doi:10.3389/fncir.2020.00022 · Cited by 26 · see citing works
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- Aristotle T. 2004. The Nicomachean Ethics Penguin Books.
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Thakare, M. R., Choudhary, P., Pydah, B., Sunke, S., Yadav, R. S. P., Agrawal, P., & Das, G. (2024) · eLife · doi:10.7554/elife.97706.1 · Cited by 3 · see citing works
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- Authors
- Weaver, K. J., Raju, S., Rucker, R. A., Chakraborty, T., Holt, R. A., & Pletcher, S. D.
- Affiliations
- University of Michigan (US)
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2023-06-16
- Volume
- 12
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W4380987446
- Cited by
- 13
- References
- 63
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 3 · 2023: 1
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Funders
- National Science Foundation (Graduate Research Fellowship Program DGE1256260)
- Howard Hughes Medical Institute (James H Gilliam Fellowships for Advanced Study GT11426)
- National Institute of Health, National Institute on Aging (R01 AG05169, R01 AG030593, R01 AG063371)
- Glenn Medical Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- hunger, food motivation, hedonic hunger, Drosophila melanogaster, mushroom body, dopaminergic neurons, feeding behavior, neuronal activity markers, optogenetic inhibition, food reward
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