Key Points
-
Mouse and fly brains contain relatively small populations of neurons that control both mating and aggression. In mice, these neurons are located within the oestrogen receptor 1-positive population in the ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl); in flies, these neurons are located within the P1 population of male-specific Fruitless-expressing interneurons in the central brain.
-
Whether the same or different neurons within each of the two systems control mating and aggression remains to be established. Also, it is not yet certain whether these neurons control both behaviours in a direct or indirect manner; for example, P1 neurons, which directly promote courtship, may trigger aggression indirectly, through a rebound from inhibition.
-
Optogenetic activation of these neuron populations evokes mating or aggressive behaviours at different threshold levels of photostimulation. However, in the two species the thresholds are reversed; whether this reflects biological or technical factors is uncertain.
-
Both populations of neurons promote persistent internal 'π' states (related to motivation, arousal or drive) that impel the animal to engage in social behaviours. Whether these states have identical functions in the two species is not yet clear.
-
Both populations receive inputs from pheromone-processing pathways, suggesting that they may transform these chemosensory cues into representations of conspecific sexual identity, internal state or behavioural decisions.
-
While the similarities between the VMHvl and the P1 cluster may be superficial and coincidental, it is attractive to think that these neuron populations represent a conserved or analogous module for the high-level control of sex and aggression. Nevertheless, there are important differences between the two systems.
Abstract
Goal-directed social behaviours such as mating and fighting are associated with scalable and persistent internal states of emotion, motivation, arousal or drive. How those internal states are encoded and coupled to behavioural decision making and action selection is not clear. Recent studies in Drosophila melanogaster and mice have identified circuit nodes that have causal roles in the control of innate social behaviours. Remarkably, in both species, these relatively small groups of neurons can influence both aggression and mating, and also play a part in the encoding of internal states that promote these social behaviours. These similarities may be superficial and coincidental, or may reflect conserved or analogous neural circuit modules for the control of social behaviours in flies and mice.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Anderson, D. J. & Adolphs, R. A framework for studying emotions across species. Cell 157, 187–200 (2014). This paper proposes that emotions can be studied in animal models as internal brain states with general properties ('primitives') that are conserved across species.
LeDoux, J. Rethinking the emotional brain. Neuron 73, 653–676 (2012). A volte-face from one of the world's leading emotion researchers arguing that 'emotions' are purely subjective phenomena, and therefore not accessible to study in animals; this article contains useful definitions of motivation, arousal and drive.
Darwin, C. The Expression of the Emotions in Man and Animals (Univ. of Chicago Press, 1872).
Lindquist, K. A., Siegel, E. H., Quigley, K. S. & Barrett, L. F. The hundred-year emotion war: are emotions natural kinds or psychological constructions? Comment on Lench, Flores, and Bench (2011). Psychol. Bull. 139, 255–263 (2011).
Dethier, V. G. The Hungry Fly: a Physiological Study of the Behavior Associated With Feeding (Harvard Univ. Press, 1976).
Berridge, K. C. Motivation concepts in behavioral neuroscience. Physiol. Behav. 81, 179–209 (2004). This excellent review describes the concepts underlying current views of motivated behaviour.
Tinbergen, N. The Study of Instinct (Clarendon Press, 1951).
Lorenz, K. & Leyhausen, P. Motivation of Human and Animal Behavior (Van Nostrand Reinhold Company, 1973).
Miczek, K. A. et al. Neurobiology of escalated aggression and violence. J. Neurosci. 27, 11803–11806 (2007).
Lorenz, K. On Aggression (Harcourt, 1966).
Palmer, C. R., Barnett, M. N., Copado, S., Gardezy, F. & Kristan, W. B. Multiplexed modulation of behavioral choice. J. Exp. Biol. 217, 2963–2973 (2014).
Palmer, C. R. & Kristan, W. B. Contextual modulation of behavioral choice. Curr. Opin. Neurobiol. 21, 520–526 (2011).
Beach, F. A. Analysis of factors involved in the arousal, maintenance and manifestation of sexual excitement in male animals. Psychosom. Med. 4, 173–198 (1942).
Devidze, N., Lee, A., Zhou, J. & Pfaff, D. CNS arousal mechanisms bearing on sex and other biologically regulated behaviors. Physiol. Behav. 88, 283–293 (2006).
Wu, M. V. & Shah, N. M. Control of masculinization of the brain and behavior. Curr. Opin. Neurobiol. 21, 116–123 (2011).
Simerly, R. B. Wired for reproduction: organization and development of sexually dimorphic circuits in the mammalian forebrain. Annu. Rev. Neurosci. 25, 507–536 (2002).
Morris, J. A., Jordan, C. L. & Breedlove, S. M. Sexual differentiation of the vertebrate nervous system. Nat. Neurosci. 7, 1034–1039 (2004).
Manoli, D. S., Fan, P., Fraser, E. J. & Shah, N. M. Neural control of sexually dimorphic behaviors. Curr. Opin. Neurobiol. 23, 330–338 (2013).
Pfaff, D., Westberg, L. & Kow, L.-M. Generalized arousal of mammalian central nervous system. J. Comp. Neurol. 493, 86–91 (2005).
Marder, E. Neuromodulation of neuronal circuits: back to the future. Neuron 76, 1–11 (2012).
Veening, J. G. et al. Do similar neural systems subserve aggressive and sexual behaviour in male rats? Insights from c-Fos and pharmacological studies. Eur. J. Pharmacol. 526, 226–239 (2005).
Koganezawa, M., Kimura, K. & Yamamoto, D. The neural circuitry that functions as a switch for courtship versus aggression in Drosophila males. Curr. Biol. 26, 1395–1403 (2016).
Yang, C. F. & Shah, N. M. Representing sex in the brain, one module at a time. Neuron 82, 261–278 (2014). This article provides a good summary of research on circuits mediating sexually dimorphic behaviours in mice.
Tinbergen, N. The hierarchical organization of nervous mechanisms underlying instinctive behaviour. Symp. Soc. Exp. Biol. 4, 305–312 (1950).
Newman, S. W. The medial extended amygdala in male reproductive behavior. A node in the mammalian social behavior network. Ann. NY Acad. Sci. 877, 242–257 (1999).
Auer, T. O. & Benton, R. Sexual circuitry in Drosophila. Curr. Opin. Neurobiol. 38, 18–26 (2016).
Hashikawa, K., Hashikawa, Y., Falkner, A. & Lin, D. The neural circuits of mating and fighting in male mice. Curr. Opin. Neurobiol. 38, 27–37 (2016).
Bayless, D. W. & Shah, N. M. Genetic dissection of neural circuits underlying sexually dimorphic social behaviours. Phil. Trans. R. Soc. B 371, 20150109 (2016).
Yamamoto, D., Sato, K. & Koganezawa, M. Neuroethology of male courtship in Drosophila: from the gene to behavior. J. Comp. Physiol. A 200, 251–264 (2014).
Yamamoto, D. & Koganezawa, M. Genes and circuits of courtship behaviour in Drosophila males. Nat. Rev. Neurosci. 14, 681–692 (2013). This paper offers an excellent introduction to fly courtship circuitry and genetics (see also reference 29).
Bargmann, C. I. & Marder, E. From the connectome to brain function. Nat. Methods 10, 483–490 (2013).
Bargmann, C. I. Beyond the connectome: how neuromodulators shape neural circuits. Bioessays 34, 458–465 (2012).
Kravitz, E. & Huber, R. Aggression in invertebrates. Curr. Opin. Neurobiol. 13, 736–743 (2003).
Huber, R., Smith, K., Delago, A., Isaksson, K. & Kravitz, E. A. Serotonin and aggressive motivation in crustaceans: altering the decision to retreat. Proc. Natl Acad. Sci. USA 94, 5939–5942 (1997).
Stevenson, P. A., Dyakonova, V., Rillich, J. & Schildberger, K. Octopamine and experience-dependent modulation of aggression in crickets. J. Neurosci. 25, 1431–1441 (2005).
Rillich, J., Schildberger, K. & Stevenson, P. A. Octopamine and occupancy: an aminergic mechanism for intruder-resident aggression in crickets. Proc. Biol. Sci. 278, 1873–1880 (2011).
Stevenson, P. A., Hofmann, H. A., Schoch, K. & Schildberger, K. The fight and flight responses of crickets depleted of biogenic amines. J. Neurobiol. 43, 107–120 (2000).
Chen, S., Lee, A. Y., Bowens, N. M., Huber, R. & Kravitz, E. A. Fighting fruit flies: a model system for the study of aggression. Proc. Natl Acad. Sci. USA 99, 5664–5668 (2002).
Hoffmann, A. A laboratory study of male territoriality in the sibling species Drosophila melanogaster and Drosophila simulans. Animal Behav. 35, 807–818 (1987).
Hoyer, S. C. et al. Octopamine in male aggression of Drosophila. Curr. Biol. 18, 159–167 (2008).
Baier, A., Wittek, B. & Brembs, B. Drosophila as a new model organism for the neurobiology of aggression? J. Exp. Biol. 205, 1233–1240 (2002).
Dierick, H. A. & Greenspan, R. J. Serotonin and neuropeptide F have opposite modulatory effects on fly aggression. Nat. Genet. 39, 678–682 (2007).
Alekseyenko, O. V. et al. Single serotonergic neurons that modulate aggression in Drosophila. Curr. Biol. 24, 2700–2707 (2014).
Alekseyenko, O. V., Chan, Y.-B., Li, R. & Kravitz, E. A. Single dopaminergic neurons that modulate aggression in Drosophila. Proc. Natl Acad. Sci. USA, 110, 6151–6156 (2013).
Certel, S. J. et al. Octopamine neuromodulatory effects on a social behavior decision-making network in Drosophila males. PLoS ONE 5, e13248 (2010).
Zhou, C. & Rao, Y. A subset of octopaminergic neurons are important for Drosophila aggression. Nat. Neurosci. 11, 1059–1067 (2008).
Andrews, J. C. et al. Octopamine neuromodulation regulates Gr32a-linked aggression and courtship pathways in Drosophila males. PLoS Genet. 10, e1004356 (2014).
Roeder, T. Tyramine and octopamine: ruling behavior and metabolism. Annu. Rev. Entomol. 50, 447–477 (2005).
Asahina, K. et al. Tachykinin-expressing neurons control male-specific aggressive arousal in Drosophila. Cell 156, 221–235 (2014).
Halasz, J. et al. Substance P neurotransmission and violent aggression: the role of tachykinin NK1 receptors in the hypothalamic attack area. Eur. J. Pharmacol. 611, 35–43 (2009).
Shaikh, M. B., Steinberg, A. & Siegel, A. Evidence that substance P is utilized in medial amygdaloid facilitation of defensive rage behavior in the cat. Brain Res. 625, 283–294 (1993).
De Felipe, C. et al. Altered nociception, analgesia and aggression in mice lacking the receptor for substance P. Nature 392, 394–397 (1998).
Coccaro, E. F., Lee, R., Owens, M. J., Kinkead, B. & Nemeroff, C. B. Cerebrospinal fluid substance P-like immunoreactivity correlates with aggression in personality disordered subjects. Biol. Psychiatry 72, 238–243 (2012).
Correa, S. M. et al. An estrogen-responsive module in the ventromedial hypothalamus selectively drives sex-specific activity in females. Cell Rep. 10, 62–74 (2015).
Lee, H. et al. Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus. Nature 509, 627–632 (2014). This article describes the functional identification of VMHvl ESR1+ neurons controlling both mounting and aggression. See also reference 99.
Taghert, P. H. & Nitabach, M. N. Peptide neuromodulation in invertebrate model systems. Neuron 76, 82–97 (2012).
Katz, P. S. & Lillvis, J. L. Reconciling the deep homology of neuromodulation with the evolution of behavior. Curr. Opin. Neurobiol. 29, 39–47 (2014).
Dickson, B. J. Wired for sex: the neurobiology of Drosophila mating decisions. Science 322, 904–909 (2008).
Manoli, D. S. et al. Male-specific fruitless specifies the neural substrates of Drosophila courtship behaviour. Nature 436, 395–400 (2005).
Stockinger, P., Kvitsiani, D., Rotkopf, S., Tirian, L. & Dickson, B. J. Neural circuitry that governs Drosophila male courtship behavior. Cell 121, 795–807 (2005). A classic paper demonstrating how manipulations of the fru locus permit genetic control of courtship circuitry in flies (see also reference 59).
Cachero, S., Ostrovsky, A. D., Yu, J. Y., Dickson, B. J. & Jefferis, G. S. X. E. Sexual dimorphism in the fly brain. Curr. Biol. 20, 1589–1601 (2010).
Yu, J. Y., Kanai, M. I., Demir, E., Jefferis, G. S. X. E. & Dickson, B. J. Cellular organization of the neural circuit that drives Drosophila courtship behavior. Curr. Biol. 20, 1602–1614 (2010).
von Philipsborn, A. C. et al. Neuronal control of Drosophila courtship song. Neuron 69, 509–522 (2011). This article provides the first example of a high-throughput neuronal-activation screen to systematically identify courtship-promoting neurons in flies.
Kohatsu, S. & Yamamoto, D. Visually induced initiation of Drosophila innate courtship-like following pursuit is mediated by central excitatory state. Nat. Commun. 6, 6457 (2015).
Kallman, B. R., Kim, H. & Scott, K. Excitation and inhibition onto central courtship neurons biases Drosophila mate choice. eLife 4, e11188 (2015).
Clowney, E. J., Iguchi, S., Bussell, J. J., Scheer, E. & Ruta, V. Multimodal chemosensory circuits controlling male courtship in Drosophila. Neuron 87, 1036–1049 (2015). This paper and reference 65 illustrate how different pheromonal inputs converge to regulate the activity of P1 neurons.
Hoopfer, E. D. Neural control of aggression in Drosophila. Curr. Opin. Neurobiol. 38, 109–118 (2016).
Kohatsu, S., Koganezawa, M. & Yamamoto, D. Female contact activates male-specific interneurons that trigger stereotypic courtship behavior in Drosophila. Neuron 69, 498–508 (2011).
Pan, Y., Meissner, G. W. & Baker, B. S. Joint control of Drosophila male courtship behavior by motion cues and activation of male-specific P1 neurons. Proc. Natl Acad. Sci. USA 109, 10065–10070 (2012).
Kimura, K.-I., Hachiya, T., Koganezawa, M., Tazawa, T. & Yamamoto, D. Fruitless and doublesex coordinate to generate male-specific neurons that can initiate courtship. Neuron 59, 759–769 (2008).
Zhou, C., Pan, Y., Robinett, C. C., Meissner, G. W. & Baker, B. S. Central brain neurons expressing doublesex regulate female receptivity in Drosophila. Neuron 83, 149–163 (2014).
Rideout, E. J., Billeter, J.-C. & Goodwin, S. F. The sex-determination genes fruitless and doublesex specify a neural substrate required for courtship song. Curr. BIol. 17, 1473–1478 (2007).
Costa, M., Manton, J. D., Ostrovsky, A. D., Prohaska, S. & Jefferis, G. S. NBLAST: rapid, sensitive comparison of neuronal structure and construction of neuron family databases. Neuron 91, 293–311 (2016).
Hoopfer, E. D., Jung, Y., Inagaki, H. K., Rubin, G. M. & Anderson, D. J. P1 interneurons promote a persistent internal state that enhances inter-male aggression in Drosophila. eLife 4, e11346 (2016). This article demonstrates that artificial activation of P1a neurons promotes aggression in addition to courtship, as well as a persistent internal state of social arousal or motivation.
Inagaki, H. K. et al. Optogenetic control of Drosophila using a red-shifted channelrhodopsin reveals experience-dependent influences on courtship. Nat. Methods 11, 325–332 (2014).
Jenett, A. et al. A GAL4-driver line resource for Drosophila neurobiology. Cell Rep. 2, 991–1001 (2012).
Hamada, F. N. et al. An internal thermal sensor controlling temperature preference in Drosophila. Nature 454, 217–220 (2008).
Luan, H., Peabody, N. C., Vinson, C. R. & White, B. H. Refined spatial manipulation of neuronal function by combinatorial restriction of transgene expression. Neuron 52, 425–436 (2006).
Pfeiffer, B. D. et al. Refinement of tools for targeted gene expression in Drosophila. Genetics 186, 735–755 (2010).
Lin, J. Y., Knutsen, P. M., Muller, A., Kleinfeld, D. & Tsien, R. Y. ReaChR: a red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation. Nat. Neurosci. 16, 1499–1508 (2013).
Klapoetke, N. C. et al. Independent optical excitation of distinct neural populations. Nat. Methods 11, 338–346 (2014).
Bath, D. E. et al. FlyMAD: rapid thermogenetic control of neuronal activity in freely walking Drosophila. Nat. Methods 11, 756–762 (2014).
Wang, L., Dankert, H., Perona, P. & Anderson, D. J. A common genetic target for environmental and heritable influences on aggressiveness in Drosophila. Proc. Natl Acad. Sci. USA 105, 5657–5663 (2008).
Zhang, S. X., Rogulja, D. & Crickmore, M. A. Dopaminergic circuitry underlying mating drive. Neuron 91, 168–181 (2016).
Beach, F. A. & Jordan, L. Sexual exhaustion and recovery in the male rat. Q. J. Exp. Psychol. 8, 121–133 (1956).
Hess, W. R. & Brügger, M. Das subkortikale Zentrum der affecktiven Abwehr-reaktion. Helv. Physiol. Acta 1, 33–52 (in German) (1943).
Siegel, A., Roeling, T. A., Gregg, T. R. & Kruk, M. R. Neuropharmacology of brain-stimulation-evoked aggression. Neurosci. Biobehav. Rev. 23, 359–389 (1999).
Kruk, M. R. in Neuroscience of Aggression ( eds Meyer-Lindenberg, A. & Miczek, K. A. ) (Springer, 2014).
Kruk, M. R. et al. Discriminant analysis of the localization of aggression-inducing electrode placements in the hypothalamus of male rats. Brain Res. 260, 61–79 (1983).
Hrabovszky, E. et al. Neurochemical characterization of hypothalamic neurons involved in attack behavior: glutamatergic dominance and co-expression of thyrotropin-releasing hormone in a subset of glutamatergic neurons. Neuroscience 133, 657–666 (2005).
Jorgenson, L. A. et al. The BRAIN Initiative: developing technology to catalyse neuroscience discovery. Phil. Trans. R. Soc. B 370, 20140164 (2015).
Nelson, R. J. & Trainor, B. C. Neural mechanisms of aggression. Nat. Rev. Neurosci. 8, 536–546 (2007).
Kruk, M. R. Ethology and pharmacology of hypothalamic aggression in the rat. Neurosci. Biobehav. Rev. 15, 527–538 (1991).
Kim, Y. et al. Mapping social behavior-induced brain activation at cellular resolution in the mouse. Cell Rep. 10, 292–305 (2015). This paper uses automated serial two-photon tomography and a genetically encoded activity reporter to produce and quantitatively compare brain-wide maps of neuronal activity during fighting and mating.
Kennedy, A. et al. Internal states and behavioral decision-making: toward an integration of emotion and cognition. Cold Spring Harb. Symp. Quant. Biol. 79, 199–210 (2015).
Anderson, D. J. Optogenetics, sex, and violence in the brain: implications for psychiatry. Biol. Psychiatry 71, 1081–1089 (2012).
Falkner, A. L. & Lin, D. Recent advances in understanding the role of the hypothalamic circuit during aggression. Front. Syst. Neurosci. 8, 168 (2014).
Lin, D. et al. Functional identification of an aggression locus in the mouse hypothalamus. Nature 470, 221–226 (2011). This is the first study to use optogenetics to control a social behaviour and to record from single VMHvl units during aggression and mating in mice.
Yang, C. F. et al. Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males. Cell 153, 896–909 (2013). This paper uses a clever genetically based cell-ablation strategy to show that VMHvl PR+ neurons (which are equivalent to ESR1+ neurons) are required for normal levels of both male aggression and mating behaviour.
Sano, K., Tsuda, M. C., Musatov, S., Sakamoto, T. & Ogawa, S. Differential effects of site-specific knockdown of estrogen receptor α in the medial amygdala, medial pre-optic area, and ventromedial nucleus of the hypothalamus on sexual and aggressive behavior of male mice. Eur. J. Neurosci. 37, 1308–1319 (2013).
Kunwar, P. S. et al. Ventromedial hypothalamic neurons control a defensive emotion state. eLife 4, e06633 (2015). This article demonstrates a scalable and threshold-dependent control of different types of defensive behaviours in a subpopulation of VMHdm/c neurons (see also reference 102).
Wang, L., Chen, I. Z. & Lin, D. Collateral pathways from the ventromedial hypothalamus mediate defensive behaviors. Neuron 85, 1–15 (2015).
Hong, W., Kim, D.-W. & Anderson, D. J. Antagonistic control of social versus repetitive self-grooming behaviors by separable amygdala neuronal subsets. Cell 158, 1348–1361 (2014).
Swanson, L. W. Anatomy of the soul as reflected in the cerebral hemispheres: neural circuits underlying voluntary control of basic motivated behaviors. J. Comp. Neurol. 493, 122–131 (2005).
Dong, H.-W., Petrovich, G. D. & Swanson, L. W. Topography of projections from amygdala to bed nuclei of the stria terminalis. Brain Res. Brain Res. Rev. 38, 192–246 (2001).
Canteras, N. S., Simerly, R. B. & Swanson, L. W. Organization of projections from the ventromedial nucleus of the hypothalamus: a Phaseolus vulgaris-leucoagglutinin study in the rat. J. Comp. Neurol. 348, 41–79 (2011).
Lee, G. & Gammie, S. C. GABAA receptor signaling in caudal periaqueductal gray regulates maternal aggression and maternal care in mice. Behav. Brain Res. 213, 230–237 (2010).
Pfaff, D. W. & Sakuma, Y. Facilitation of the lordosis reflex of female rats from the ventromedial nucleus of the hypothalamus. J. Physiol. 288, 189–202 (1979).
Pfaff, D. W. & Sakuma, Y. Deficit in the lordosis reflex of female rats caused by lesions in the ventromedial nucleus of the hypothalamus. J. Physiol. 288, 203–210 (1979).
Falkner, A. L., Dollar, P., Perona, P., Anderson, D. J. & Lin, D. Decoding ventromedial hypothalamic neural activity during male mouse aggression. J. Neurosci. 34, 5971–5984 (2014).
Goldman, M., Compte, A. & Wang, X.-J. in New Encyclopedia of Neuroscience (ed. Squire, L. R.) 1–26 (Elsevier, 2007).
Ginsburg, B. & Allee, W. Some effects of conditioning on social dominance and subordination in inbred strains of mice. Physiol. Zool. 15, 485–506 (1942).
Couppis, M. H. & Kennedy, C. H. The rewarding effect of aggression is reduced by nucleus accumbens dopamine receptor antagonism in mice. Psychopharmacology 197, 449–456 (2008).
Falkner, A. L., Grosenick, L., Davidson, T. J., Deisseroth, K. & Lin, D. Hypothalamic control of male aggression-seeking behavior. Nat. Neurosci. 19, 596–604 (2016). This paper demonstrates that VMHvl neurons are activated during the 'seeking' phase of an aggressive encounter and that manipulation of their activity can accelerate or inhibit nose poking to gain access to a subordinate male.
Potegal, M., Hebert, M., DeCoster, M. & Meyerhoff, J. L. Brief, high-frequency stimulation of the corticomedial amygdala induces a delayed and prolonged increase of aggressiveness in male Syrian golden hamsters. Behav. Neurosci. 110, 401–412 (1996).
Potegal, M. Time course of aggressive arousal in female hamsters and male rats. Behav. Neural Biol. 58, 120–124 (1992).
Spiteri, T. et al. Estrogen-induced sexual incentive motivation, proceptivity and receptivity depend on a functional estrogen receptor α in the ventromedial nucleus of the hypothalamus but not in the amygdala. Neuroendocrinology 91, 142–154 (2010).
de Velasco, B. et al. Specification and development of the pars intercerebralis and pars lateralis, neuroendocrine command centers in the Drosophila brain. Dev. Biol. 302, 309–323 (2007).
Ziv, Y. et al. Long-term dynamics of CA1 hippocampal place codes. Nat. Neurosci. 16, 264–266 (2013).
Jennings, J. H. et al. Visualizing hypothalamic network dynamics for appetitive and consummatory behaviors. Cell 160, 516–527 (2015). This is the first paper to use microendoscopic imaging to monitor population activity among genetically defined hypothalamic neurons in freely behaving animals.
Tasic, B. et al. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat. Neurosci. 19, 335–346 (2016).
Macosko, E. Z. et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161, 1202–1214 (2015).
von Holst, E. & von Saint Paul, U. On the functional organization of drives. J. Animal Behav. 11, 1–20 (1960).
Grover, D., Katsuki, T. & Greenspan, R. J. Flyception: imaging brain activity in freely walking fruit flies. Nat. Methods 13, 569–572 (2016).
Dong, H.-W. & Swanson, L. W. Projections from bed nuclei of the stria terminalis, posterior division: implications for cerebral hemisphere regulation of defensive and reproductive behaviors. J. Comp. Neurol. 471, 396–433 (2004).
Dulac, C. & Wagner, S. Genetic analysis of brain circuits underlying pheromone signaling. Annu. Rev. Genet. 40, 449–467 (2006).
Toth, M., Fuzesi, T., Halász, J., Tulogdi, A. & Haller, J. Neural inputs of the hypothalamic “aggression area” in the rat. Behav. Brain Res. 215, 7–20 (2010).
Root, C. M., Denny, C. A., Hen, R. & Axel, R. The participation of cortical amygdala in innate, odour-driven behaviour. Nature 515, 269–273 (2014).
Mandiyan, V. S., Coats, J. K. & Shah, N. M. Deficits in sexual and aggressive behaviors in Cnga2 mutant mice. Nat. Neurosci. 8, 1660–1662 (2005).
Yoon, H., Enquist, L. W. & Dulac, C. Olfactory inputs to hypothalamic neurons controlling reproduction and fertility. Cell 123, 669–682 (2005).
Leypold, B. G. et al. Altered sexual and social behaviors in trp2 mutant mice. Proc. Natl Acad. Sci. USA 99, 6376–6381 (2002).
Stowers, L., Holy, T. E., Meister, M., Dulac, C. & Koentges, G. Loss of sex discrimination and male-male aggression in mice deficient for TRP2. Science 295, 1493–1500 (2002).
Sachs, B. D. Erection evoked in male rats by airborne scent from estrous females. Physiol. Behav. 62, 921–924 (1997).
Bensafi, M., Tsutsui, T., Khan, R., Levenson, R. W. & Sobel, N. Sniffing a human sex-steroid derived compound affects mood and autonomic arousal in a dose-dependent manner. Psychoneuroendocrinology 29, 1290–1299 (2004).
Simerly, R. B., Chang, C., Muramatsu, M. & Swanson, L. W. Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: an in situ hybridization study. J. Comp. Neurol. 294, 76–95 (1990).
Shohat-Ophir, G., Kaun, K. R., Azanchi, R. & Heberlein, U. Sexual deprivation increases ethanol intake in Drosophila. Science 335, 1351–1355 (2012).
Kristan, W. B. Neuronal decision-making circuits. Curr. Biol. 18, R928–R932 (2008).
Kim, C. K. et al. Simultaneous fast measurement of circuit dynamics at multiple sites across the mammalian brain. Nat. Methods 13, 325–328 (2016).
van Swinderen, B. & Andretic, R. Arousal in Drosophila. Behav. Processes 64, 133–144 (2003).
Lebestky, T. et al. Two different forms of arousal in Drosophila are oppositely regulated by the dopamine D1 receptor ortholog DopR via distinct neural circuits. Neuron 64, 522–536 (2009).
Sternson, S. M. Hypothalamic survival circuits: blueprints for purposive behaviors. Neuron 77, 810–824 (2013).
Castro, D. C. & Berridge, K. C. Advances in the neurobiological bases for food 'liking' versus 'wanting'. Physiol. Behav. 136, 22–30 (2014).
Berridge, K. C. Measuring hedonic impact in animals and infants: microstructure of affective taste reactivity patterns. Neurosci. Biobehav. Rev. 24, 173–198 (2000).
Wustmann, G., Rein, K., Wolf, R. & Heisenberg, M. A new paradigm for operant conditioning of Drosophila melanogaster. J. Comp. Physiol. A 179, 429–436 (1996).
Kaun, K. R., Azanchi, R., Maung, Z., Hirsh, J. & Heberlein, U. A Drosophila model for alcohol reward. Nat. Neurosci. 14, 612–619 (2011).
Krashes, M. J. et al. A neural circuit mechanism integrating motivational state with memory expression in Drosophila. Cell 139, 416–427 (2009).
Dolan, R. J. Emotion, cognition, and behavior. Science 298, 1191–1194 (2002).
Wu, M. V. et al. Estrogen masculinizes neural pathways and sex-specific behaviors. Cell 139, 61–72 (2009).
Kohl, J., Ostrovsky, A. D., Frechter, S. & Jefferis, G. S. X. E. A bidirectional circuit switch reroutes pheromone signals in male and female brains. Cell 155, 1610–1623 (2013).
Ruta, V. et al. A dimorphic pheromone circuit in Drosophila from sensory input to descending output. Nature 468, 686–690 (2010).
Acknowledgements
The author thanks D. Tsao, E. Hoopfer and members of the Anderson laboratory, and an anonymous reviewer for helpful discussions and critical feedback, and V. Chiu for fly drawings in figures 1 and 3. The author apologizes to all of those authors whose primary research papers could not be cited owing to restrictions on the number of references. This work was supported by grants from the US National Institutes of Health and National Institute of Mental Health, the Paul G. Allen Family Foundation, the Simons Foundation, the Ellison Medical Foundation, the Moore Foundation, the Guggenheim Foundation and the California Institute of Technology. D.J.A. is an investigator of the Howard Hughes Medical Institute.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The author declares no competing financial interests.
Glossary
- π states
-
A generic term, introduced for the purposes of this Review, denoting persistent and scalable internal brain states.
- Appetitive phases
-
The phases of a goal-directed activity that involve seeking or investigative actions; in social behaviour, these include approach and ano-genital or head-directed sniffing.
- Consummatory phases
-
In aggression, the phase that involves overt attack behaviours such as biting; in mating, the phase that includes intromission (pelvic thrusting with vaginal penetration) and ejaculation.
- Scalability
-
In the context of this Review, the property of a π state to exhibit graded and time-varying changes in its intensity, such as escalation during a social encounter.
- Gal4 lines
-
Inbred lines of transgenic flies in which the expression of the yeast transcriptional activator Gal4 is restricted to specific neuron subsets by regulatory DNA fragments.
- Split Gal4 system
-
Intersectional labelling of neurons by expressing the DNA-binding and transcriptional activation domains of GAL4 from two separate transgenes under the control of different but overlapping promoters.
- Wing extension
-
A social behaviour in which a male fly extends one wing towards another fly and vibrates it at specific frequencies to generate a courtship 'song'.
- Fos
-
An immediate early gene, the transcription of which is rapidly induced by elevated intracellular free calcium and therefore serves as a surrogate marker of neuronal activation.
- Fibres of passage
-
Axons that pass through a given brain region en route to a distant target without forming local synapses; such axons can nevertheless be electrically stimulated.
- Compartment analysis of temporal activity by fluorescence in situ hybridization
-
(catFISH). A method for comparing immediate-early gene activation in the same neuron in response to two sequential stimuli.
Rights and permissions
About this article
Cite this article
Anderson, D. Circuit modules linking internal states and social behaviour in flies and mice. Nat Rev Neurosci 17, 692–704 (2016). https://doi.org/10.1038/nrn.2016.125
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrn.2016.125
This article is cited by
-
Social circuits and their dysfunction in autism spectrum disorder
Molecular Psychiatry (2023)
-
All-optical closed-loop voltage clamp for precise control of muscles and neurons in live animals
Nature Communications (2023)
-
Neural circuits regulating prosocial behaviors
Neuropsychopharmacology (2023)
-
Effects of lithium on aggression in Drosophila
Neuropsychopharmacology (2023)
-
Defensive and offensive behaviours in a Kleefstra syndrome mouse model
Animal Cognition (2023)
