首页 » 文章 » 文章详细信息
eLife Volume 9 ,2020-04-11
A neuropeptide regulates fighting behavior in Drosophila melanogaster
Fengming Wu 1 , 2 Bowen Deng 3 , 4 Na Xiao 5 Tao Wang 1 , 6 Yining Li 3 , 7 Rencong Wang 1 , 2 Kai Shi 1 , 2 Dong-Gen Luo 4 , 5 Yi Rao 3 , 4 , 7 Chuan Zhou 1 , 2 , 4
Show affiliations
Received 2019-12-06, accepted for publication 2020-04-11, Published 2020-04-11

Aggressive behavior is regulated by various neuromodulators such as neuropeptides and biogenic amines. Here we found that the neuropeptide Drosulfakinin (Dsk) modulates aggression in Drosophila melanogaster. Knock-out of Dsk or Dsk receptor CCKLR-17D1 reduced aggression. Activation and inactivation of Dsk-expressing neurons increased and decreased male aggressive behavior, respectively. Moreover, data from transsynaptic tracing, electrophysiology and behavioral epistasis reveal that Dsk-expressing neurons function downstream of a subset of P1 neurons (P1a-splitGAL4) to control fighting behavior. In addition, winners show increased calcium activity in Dsk-expressing neurons. Conditional overexpression of Dsk promotes social dominance, suggesting a positive correlation between Dsk signaling and winning effects. The mammalian ortholog CCK has been implicated in mammal aggression, thus our work suggests a conserved neuromodulatory system for the modulation of aggressive behavior.


D. melanogaster;social hierarchy;neural circuit;neuropeptide


© 2020, Wu et al
http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.


Fengming Wu,Bowen Deng,Na Xiao,Tao Wang,Yining Li,Rencong Wang,Kai Shi,Dong-Gen Luo,Yi Rao,Chuan Zhou. A neuropeptide regulates fighting behavior in Drosophila melanogaster. eLife ,Vol.9(2020)



[1] Q Li, X Deng, P Singh. (2007). Significant increase in the aggressive behavior of transgenic mice overexpressing peripheral progastrin peptides: associated changes in CCK2 and serotonin receptors in the CNS. Neuropsychopharmacology.32:1813-1821. DOI: 10.1073/pnas.1303446110.
[2] MD Gordon, K Scott. (2009). Motor control in a taste circuit. Neuron.61:373-384. DOI: 10.1073/pnas.1303446110.
[3] XJ Gao, O Riabinina, J Li, CJ Potter. et al.(2015). A transcriptional reporter of intracellular ca(2+) in. Nature Neuroscience.18:917-925. DOI: 10.1073/pnas.1303446110.
[4] E Vrontou, SP Nilsen, E Demir, EA Kravitz. et al.(2006). Fruitless regulates aggression and dominance in. Nature Neuroscience.9:1469-1471. DOI: 10.1073/pnas.1303446110.
[5] M Versteven, L Vanden Broeck, B Geurten, L Zwarts. et al.(2017). Hearing regulates aggression. PNAS.114:1958-1963. DOI: 10.1073/pnas.1303446110.
[6] RN Arey, JF Enwright, SM Spencer, E Falcon. et al.(2014). An important role for cholecystokinin, a CLOCK target gene, in the development and treatment of manic-like behaviors. Molecular Psychiatry.19:342-350. DOI: 10.1073/pnas.1303446110.
[7] I Tõru, A Aluoja, Ülle Võhma, M Raag. et al.(2010). Associations between personality traits and CCK-4-induced panic attacks in healthy volunteers. Psychiatry Research.178:342-347. DOI: 10.1073/pnas.1303446110.
[8] OV Alekseyenko, YB Chan, MP Fernandez, T Bülow. et al.(2014). Single serotonergic neurons that modulate aggression in. Current Biology.24:2700-2707. DOI: 10.1073/pnas.1303446110.
[9] Y Pan, GW Meissner, BS Baker. (2012). Joint control of male courtship behavior by motion cues and activation of male-specific P1 neurons. PNAS.109:10065-10070. DOI: 10.1073/pnas.1303446110.
[10] T Rohlfing, CR Maurer. (2003). Nonrigid image registration in shared-memory multiprocessor environments with application to brains, breasts, and bees. IEEE Transactions on Information Technology in Biomedicine.7:16-25. DOI: 10.1073/pnas.1303446110.
[11] OV Alekseyenko, Y-B Chan, R Li, EA Kravitz. et al.(2013). Single dopaminergic neurons that modulate aggression in. PNAS.110:6151-6156. DOI: 10.1073/pnas.1303446110.
[12] FN Hamada, M Rosenzweig, K Kang, SR Pulver. et al.(2008). An internal thermal sensor controlling temperature preference in. Nature.454:217-220. DOI: 10.1073/pnas.1303446110.
[13] EA Kravitz, R Huber. (2003). Aggression in invertebrates. Current Opinion in Neurobiology.13:736-743. DOI: 10.1073/pnas.1303446110.
[14] C Sears, J Wilson, A Fitches. (2013). Investigating the role of BDNF and CCK system genes in suicidality in a familial bipolar cohort. Journal of Affective Disorders.151:611-617. DOI: 10.1073/pnas.1303446110.
[15] TM Kubiak, MJ Larsen, KJ Burton, CA Bannow. et al.(2002). Cloning and functional expression of the sulfakinin receptor DSK-R1. Biochemical and Biophysical Research Communications.291:313-320. DOI: 10.1073/pnas.1303446110.
[16] AA Hoffmann. (1987). Territorial encounters between males of different sizes. Animal Behaviour.35:1899-1901. DOI: 10.1073/pnas.1303446110.
[17] AA Hoffmann. (1990). The influence of age and experience with conspecifics on territorial behavior. Journal of Insect Behavior.3:1-12. DOI: 10.1073/pnas.1303446110.
[18] L Wang, DJ Anderson. (2010). Identification of an aggression-promoting pheromone and its receptor neurons in. Nature.463:227-231. DOI: 10.1073/pnas.1303446110.
[19] AJ Brake, MJ Wagenbach, D Julius. (1994). New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor. Nature.371:519-523. DOI: 10.1073/pnas.1303446110.
[20] K Watanabe, H Chiu, BD Pfeiffer, AM Wong. et al.(2017). A circuit node that integrates convergent input from neuromodulatory and social Behavior-Promoting neurons to control aggression in. Neuron.95:1112-1128. DOI: 10.1073/pnas.1303446110.
[21] L Wang, X Han, J Mehren, M Hiroi. et al.(2011). Hierarchical chemosensory regulation of male-male social interactions in. Nature Neuroscience.14:757-762. DOI: 10.1073/pnas.1303446110.
[22] C Becker, MH Thièbot, Y Touitou, M Hamon. et al.(2001). Enhanced cortical extracellular levels of cholecystokinin-like material in a model of anticipation of social defeat in the rat. The Journal of Neuroscience.21:262-269. DOI: 10.1073/pnas.1303446110.
[23] SJ Certel, MG Savella, DC Schlegel, EA Kravitz. et al.(2007). Modulation of male behavioral choice. PNAS.104:4706-4711. DOI: 10.1073/pnas.1303446110.
[24] K Asahina. (2017). Neuromodulation and strategic action choice in Aggression. Annual Review of Neuroscience.40:51-75. DOI: 10.1073/pnas.1303446110.
[25] S Chen, AY Lee, NM Bowens, R Huber. et al.(2002). Fighting fruit flies: a model system for the study of aggression. PNAS.99:5664-5668. DOI: 10.1073/pnas.1303446110.
[26] K Asahina, K Watanabe, BJ Duistermars, E Hoopfer. et al.(2014). Tachykinin-expressing neurons control male-specific aggressive arousal in. Cell.156:221-235. DOI: 10.1073/pnas.1303446110.
[27] C Darwin. (1859). On the Origin of Species by Means of Natural Selection. DOI: 10.1073/pnas.1303446110.
[28] KZ Lorenz. (1963). On aggression. DOI: 10.1073/pnas.1303446110.
[29] AA Hoffmann, Z Cacoyianni. (1989). Selection for territoriality in : correlated responses in mating success and other fitness components. Animal Behaviour.38:23-34. DOI: 10.1073/pnas.1303446110.
[30] AA Hoffmann, Z Cacoyianni. (1990). Territoriality in as a conditional strategy. Animal Behaviour.40:526-537. DOI: 10.1073/pnas.1303446110.
[31] W Liu, X Liang, J Gong, Z Yang. et al.(2011). Social regulation of aggression by pheromonal activation of Or65a olfactory neurons in. Nature Neuroscience.14:896-902. DOI: 10.1073/pnas.1303446110.
[32] B Luo, JW Cheu, A Siegel. (1998). Cholecystokinin B receptors in the periaqueductal gray potentiate defensive rage behavior elicited from the medial hypothalamus of the cat. Brain Research.796:27-37. DOI: 10.1073/pnas.1303446110.
[33] SC Hoyer, A Eckart, A Herrel, T Zars. et al.(2008). Octopamine in male aggression of . Curr Biol.18:159-167. DOI: 10.1073/pnas.1303446110.
[34] A Yurkovic, O Wang, AC Basu, EA Kravitz. et al.(2006). Learning and memory associated with aggression in. PNAS.103:17519-17524. DOI: 10.1073/pnas.1303446110.
[35] ED Hoopfer, Y Jung, HK Inagaki, GM Rubin. et al.(2015). P1 interneurons promote a persistent internal state that enhances inter-male aggression in. eLife.4. DOI: 10.1073/pnas.1303446110.
[36] X Zhang, J Qi, N Tang, S Wang. et al.(2018). Intraperitoneal injection of nesfatin-1 primarily through the CCK-CCK1R signal pathway affects expression of appetite factors to inhibit the food intake of siberian sturgeon (Acipenser baerii). Peptides.109:14-22. DOI: 10.1073/pnas.1303446110.
[37] CJ Shen, D Zheng, KX Li, JM Yang. et al.(2019). Cannabinoid CB receptors in the amygdalar cholecystokinin glutamatergic afferents to nucleus accumbens modulate depressive-like behavior. Nature Medicine.25:337-349. DOI: 10.1073/pnas.1303446110.
[38] W Sf, C Guo, H Zhao, MS Sun. et al.(2019). Drosulfakinin/CCKLR signaling in 1 fruitless circuitry antagonizes P1 neurons to regulate sexual arousal in. Nature Communications.10. DOI: 10.1073/pnas.1303446110.
[39] A Siegel, KL Schubert, MB Shaikh. (1997). Neurotransmitters regulating defensive rage behavior in the cat. Neuroscience & Biobehavioral Reviews.21:733-742. DOI: 10.1073/pnas.1303446110.
[40] HA Dierick, RJ Greenspan. (2007). Serotonin and neuropeptide F have opposite modulatory effects on fly aggression. Nature Genetics.39:678-682. DOI: 10.1073/pnas.1303446110.
[41] DR Nässel, MJ Williams. (2014). Cholecystokinin-Like peptide (DSK) in , not only for satiety signaling. Frontiers in Endocrinology.5. DOI: 10.1073/pnas.1303446110.
[42] S Diegelmann, A Jansen, S Jois, K Kastenholz. et al.(2017). The CApillary FEeder assay measures food intake in . Journal of Visualized Experiments : JoVE.121. DOI: 10.1073/pnas.1303446110.
[43] B Deng, Q Li, X Liu, Y Cao. et al.(2019). Chemoconnectomics: mapping chemical transmission in. Neuron.101:876-893. DOI: 10.1073/pnas.1303446110.
[44] C Becker, B Zeau, C Rivat, A Blugeot. et al.(2008). Repeated social defeat-induced depression-like behavioral and biological alterations in rats: involvement of cholecystokinin. Molecular Psychiatry.13:1079-1092. DOI: 10.1073/pnas.1303446110.
[45] H Watkins, CE Seidman, JG Seidman, HS Feng. et al.(1996). Expression and functional assessment of a truncated cardiac troponin T that causes hypertrophic cardiomyopathy. evidence for a dominant negative action. Journal of Clinical Investigation.98:2456-2461. DOI: 10.1073/pnas.1303446110.
[46] M Beye, P Neumann, M Chapuisat, P Pamilo. et al.(1998). Nestmate recognition and the genetic relatedness of nests in the ant Formica pratensis. Behavioral Ecology and Sociobiology.43:67-72. DOI: 10.1073/pnas.1303446110.
[47] R Nichols, SA Schneuwly, JE Dixon. (1988). Identification and characterization of a homologue to the vertebrate neuropeptide cholecystokinin. The Journal of Biological Chemistry.263:12167-12170. DOI: 10.1073/pnas.1303446110.
[48] SP Nilsen, YB Chan, R Huber, EA Kravitz. et al.(2004). Gender-selective patterns of aggressive behavior in. PNAS.101:12342-12347. DOI: 10.1073/pnas.1303446110.
[49] MJ Williams, P Goergen, J Rajendran, G Zheleznyakova. et al.(2014). Obesity-linked homologues TfAP-2 and twz establish meal frequency in. PLOS Genetics.10. DOI: 10.1073/pnas.1303446110.
[50] J Bradwejn, D Koszycki, G Meterissian. (1990). Tetrapeptide induces panic attack stetrapeptide induces panic attacks in patients with panic disorder . The Canadian Journal of Psychiatry.35:83-85. DOI: 10.1073/pnas.1303446110.
[51] A Nern, BD Pfeiffer, GM Rubin. (2015). Optimized tools for multicolor stochastic labeling reveal diverse stereotyped cell arrangements in the fly visual system. PNAS.112:E2967-E2976. DOI: 10.1073/pnas.1303446110.
[52] GS Jefferis, CJ Potter, AM Chan, EC Marin. et al.(2007). Comprehensive maps of higher olfactory centers: spatially segregated fruit and pheromone representation. Cell.128:1187-1203. DOI: 10.1073/pnas.1303446110.
[53] A Keller, ST Sweeney, T Zars, CJ O'Kane. et al.(2002). Targeted expression of tetanus neurotoxin interferes with behavioral responses to sensory input in. Journal of Neurobiology.50:221-233. DOI: 10.1073/pnas.1303446110.
[54] YK Kim, M Saver, J Simon, CF Kent. et al.(2018). Repetitive aggressive encounters generate a long-lasting internal state in males. PNAS.115:1099-1104. DOI: 10.1073/pnas.1303446110.
[55] Y Jung, A Kennedy, H Chiu, F Mohammad. et al.(2020). Neurons that function within an integrator to promote a persistent behavioral state in .  Neuron.333. DOI: 10.1073/pnas.1303446110.
[56] ST Sweeney, K Broadie, J Keane, H Niemann. et al.(1995). Targeted expression of tetanus toxin light chain in specifically eliminates synaptic transmission and causes behavioral defects. Neuron.14:341-351. DOI: 10.1073/pnas.1303446110.
[57] MLL Donnelly, LE Hughes, G Luke, H Mendoza. et al.(2001). The 'cleavage' activities of foot-and-mouth disease virus 2A site-directed mutants and naturally occurring '2A-like' sequences. Journal of General Virology.82:1027-1041. DOI: 10.1073/pnas.1303446110.
[58] M Talay, EB Richman, NJ Snell, GG Hartmann. et al.(2017). Transsynaptic mapping of Second-Order taste neurons in flies by trans-Tango. Neuron.96:783-795. DOI: 10.1073/pnas.1303446110.
[59] AS Thum, S Knapek, J Rister, E Dierichs-Schmitt. et al.(2006). Differential potencies of effector genes in adult. The Journal of Comparative Neurology.498:194-203. DOI: 10.1073/pnas.1303446110.
[60] EH Feinberg, MK Vanhoven, A Bendesky, G Wang. et al.(2008). GFP reconstitution across synaptic partners (GRASP) defines cell contacts and synapses in living nervous systems. Neuron.57:353-363. DOI: 10.1073/pnas.1303446110.
[61] BJ Duistermars, BD Pfeiffer, ED Hoopfer, DJ Anderson. et al.(2018). A brain module for scalable control of complex, Multi-motor threat displays. Neuron.100:1474-1490. DOI: 10.1073/pnas.1303446110.
[62] AH Sturtevant. (1915). Experiments on sex recognition and the problem of sexual selection in . Anim Behav.5:351-366. DOI: 10.1073/pnas.1303446110.
[63] C Zhou, Y Rao, Y Rao. (2008). A subset of octopaminergic neurons are important for aggression. Nature Neuroscience.11:1059-1067. DOI: 10.1073/pnas.1303446110.
[64] C Zhou, R Franconville, AG Vaughan, CC Robinett. et al.(2015). Central neural circuitry mediating courtship song perception in male. eLife.4. DOI: 10.1073/pnas.1303446110.
[65] M Koganezawa, K Kimura, D Yamamoto. (2016). The neural circuitry that functions as a switch for courtship versus aggression in males. Current Biology.26:1395-1403. DOI: 10.1073/pnas.1303446110.