Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Encoding asymmetry within neural circuits

Key Points

  • Asymmetries between the left and right sides of the nervous system are present throughout the animal kingdom, from invertebrates to mammals.

  • There are two fundamentally distinct ways in which neural circuits can be lateralized: one involves specification of common components on both sides, but to different extents. The other involves unilateral structures, which are present exclusively on one side.

  • Both environmental and genetic factors contribute to the development of neural asymmetries. Research in model organisms is beginning to reveal the molecular-genetic pathways that control the development of brain lateralization.

  • Theoretical advantages of brain asymmetry include the capacity for parallel processing, the specialization of left and right sides for distinct computations and the restriction of information processing within local circuits characterized by short, fast axonal connections. However, at present we do not understand the specific functions of the majority of known circuit asymmetries.

  • Recent technological advances that allow neural activity to be measured and manipulated during behaviour have enormous potential to reveal the functions of asymmetric circuits. Furthermore, large-scale projects that are defining brain anatomy and connectivity in unprecedented detail will help to reveal the circuit organization responsible for functional and behavioural lateralization.

Abstract

Genetic and environmental factors control morphological and functional differences between the two sides of the nervous system. Neural asymmetries are proposed to have important roles in circuit physiology, cognition and species-specific behaviours. We propose two fundamentally different mechanisms for encoding left–right asymmetry in neural circuits. In the first, asymmetric circuits share common components; in the second, there are unique unilateral structures. Research in both vertebrates and invertebrates is helping to reveal the mechanisms underlying the development of neural lateralization, but less is known about the function of circuit asymmetries. Technical advances in the coming years are likely to revolutionize our understanding of left–right asymmetry in the nervous system.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Classes of asymmetric neural circuitry.
Figure 2: Light-induced visual lateralization in birds.
Figure 3: Circuit asymmetries associated with the zebrafish epithalamus.
Figure 4: Sensory asymmetries and the computation of chemotaxis in worms.

Similar content being viewed by others

References

  1. Young, R. E. & Govind, C. K. Neural asymmetry in male fiddler crabs. Brain Res. 280, 251–262 (1983).

    Article  CAS  PubMed  Google Scholar 

  2. Sun, T. in The Two Halves Of The Brain. Information Processing In The Cerebral Hemispheres (eds Hugdahl, K. & Westerfield, M.) 21–36 (MIT Press, 2010).

    Book  Google Scholar 

  3. Corballis, M. C. The evolution and genetics of cerebral asymmetry. Phil. Trans. R. Soc. B 364, 867–879 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. Takao, H., Hayashi, N. & Ohtomo, K. White matter asymmetry in healthy individuals: a diffusion tensor imaging study using tract-based spatial statistics. Neuroscience 193, 291–299 (2011).

    Article  CAS  PubMed  Google Scholar 

  5. Takao, H. et al. Gray and white matter asymmetries in healthy individuals aged 21–29 years: a voxel-based morphometry and diffusion tensor imaging study. Hum. Brain Mapp. 32, 1762–1773 (2011).

    Article  PubMed  Google Scholar 

  6. Thiebaut de Schotten, M. et al. Atlasing location, asymmetry and inter-subject variability of white matter tracts in the human brain with MR diffusion tractography. Neuroimage 54, 49–59 (2011).

    Article  PubMed  Google Scholar 

  7. Thiebaut de Schotten, M. et al. A lateralized brain network for visuospatial attention. Nature Neurosci. 14, 1245–1246 (2011). This paper demonstrates that asymmetries in the parieto-frontal network of humans enhance performance in visuospatial attention.

    Article  CAS  PubMed  Google Scholar 

  8. Powell, H. W. et al. Hemispheric asymmetries in language-related pathways: a combined functional MRI and tractography study. Neuroimage 32, 388–399 (2006).

    Article  PubMed  Google Scholar 

  9. Putnam, M. C., Steven, M. S., Doron, K. W., Riggall, A. C. & Gazzaniga, M. S. Cortical projection topography of the human splenium: hemispheric asymmetry and individual differences. J. Cogn. Neurosci. 22, 1662–1669 (2010).

    Article  PubMed  Google Scholar 

  10. Koch, G. et al. Asymmetry of parietal interhemispheric connections in humans. J. Neurosci. 31, 8967–8975 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Shinohara, Y. et al. Left-right asymmetry of the hippocampal synapses with differential subunit allocation of glutamate receptors. Proc. Natl Acad. Sci. USA 105, 19498–19503 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kawakami, R. et al. Asymmetrical allocation of NMDA receptor ɛ2 subunits in hippocampal circuitry. Science 300, 990–994 (2003). References 11 and 12 provided a molecular basis for the structural and functional asymmetry of the hippocampus at the synaptic level.

    Article  CAS  PubMed  Google Scholar 

  13. Kohl, M. M. et al. Hemisphere-specific optogenetic stimulation reveals left-right asymmetry of hippocampal plasticity. Nature Neurosci. 14, 1413–1415 (2011). Using optogentic tools, this paper shows that asymmetries at the synaptic level lead to differences in hippocampal plasticity between left and right.

    Article  CAS  PubMed  Google Scholar 

  14. Kawakami, R., Dobi, A., Shigemoto, R. & Ito, I. Right isomerism of the brain in inversus viscerum mutant mice. PLoS ONE 3, e1945 (2008).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Goto, K. et al. Left-right asymmetry defect in the hippocampal circuitry impairs spatial learning and working memory in iv mice. PLoS ONE 5, e15468 (2010).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Shinohara, Y. et al. Right-hemispheric dominance of spatial memory in split-brain mice. Hippocampus 22, 117–121 (2012).

    Article  PubMed  Google Scholar 

  17. Hobert, O., Johnston, R. J. Jr & Chang, S. Left−right asymmetry in the nervous system: the Caenorhabditis elegans model. Nature Rev. Neurosci. 3, 629–640 (2002).

    Article  CAS  Google Scholar 

  18. Chapple, W. D. Central and peripheral origins of asymmetry in the abdominal motor system of the hermit crab. Ann. NY Acad. Sci. 299, 43–58 (1977).

    Article  Google Scholar 

  19. Pascual, A., Huang, K. L., Neveu, J. & Preat, T. Neuroanatomy: brain asymmetry and long-term memory. Nature 427, 605–606 (2004).

    Article  CAS  PubMed  Google Scholar 

  20. White, J. G., Southgate, E., Thomson, J. N. & Brenner, S. The structure of the nervous system of the nematode Caenorhabditis elegans. Phil. Trans. R. Soc. Lond. B 314, 1–340 (1986).

    Article  CAS  Google Scholar 

  21. Troemel, E. R., Sagasti, A. & Bargmann, C. I. Lateral signaling mediated by axon contact and calcium entry regulates asymmetric odorant receptor expression in C. elegans. Cell 99, 387–398 (1999).

    Article  CAS  PubMed  Google Scholar 

  22. Jenett, A. et al. A GAL4-driver line resource for Drosophila neurobiology. Cell Rep. 2, 991–1001 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Mormann, F. et al. A category-specific response to animals in the right human amygdala. Nature Neurosci. 14, 1247–1249 (2011).

    Article  CAS  PubMed  Google Scholar 

  24. Kanwal, J. S. Right-left asymmetry in the cortical processing of sounds for social communication versus navigation in mustached bats. Eur. J. Neurosci. 35, 257–270 (2012).

    Article  PubMed  Google Scholar 

  25. Briggman, K. L., Helmstaedter, M. & Denk, W. Wiring specificity in the direction-selectivity circuit of the retina. Nature 471, 183–188 (2011).

    CAS  PubMed  Google Scholar 

  26. Tye, K. M. & Deisseroth, K. Optogenetic investigation of neural circuits underlying brain disease in animal models. Nature Rev. Neurosci. 13, 251–266 (2012).

    Article  CAS  Google Scholar 

  27. Weidner, C., Reperant, J., Miceli, D., Haby, M. & Rio, J. P. An anatomical study of ipsilateral retinal projections in the quail using radioautographic, horseradish peroxidase, fluorescence and degeneration techniques. Brain Res. 340, 99–108 (1985).

    Article  CAS  PubMed  Google Scholar 

  28. Koshiba, M., Nakamura, S., Deng, C. & Rogers, L. J. Light-dependent development of asymmetry in the ipsilateral and contralateral thalamofugal visual projections of the chick. Neurosci. Lett. 336, 81–84 (2003).

    Article  CAS  PubMed  Google Scholar 

  29. Rogers, L. J. & Deng, C. Light experience and lateralization of the two visual pathways in the chick. Behav. Brain Res. 98, 277–287 (1999).

    Article  CAS  PubMed  Google Scholar 

  30. Rogers, L. J. & Sink, H. S. Transient asymmetry in the projections of the rostral thalamus to the visual hyperstriatum of the chicken, and reversal of its direction by light exposure. Exp. Brain Res. 70, 378–384 (1988). An early study that provides neuroanatomical evidence for the formation of asymmetric connectivity in the visual pathway in response to light stimulation.

    Article  CAS  PubMed  Google Scholar 

  31. Dharmaretnam, M. & Rogers, L. J. Hemispheric specialization and dual processing in strongly versus weakly lateralized chicks. Behav. Brain Res. 162, 62–70 (2005).

    Article  CAS  PubMed  Google Scholar 

  32. Mench, J. A. & Andrew, R. J. Lateralization of a food search task in the domestic chick. Behav. Neural Biol. 46, 107–114 (1986).

    Article  CAS  PubMed  Google Scholar 

  33. Rogers, L. J. Evolution of hemispheric specialization: advantages and disadvantages. Brain Lang. 73, 236–253 (2000).

    Article  CAS  PubMed  Google Scholar 

  34. Rogers, L. J., Andrew, R. J. & Johnston, A. N. Light experience and the development of behavioural lateralization in chicks: III. Learning to distinguish pebbles from grains. Behav. Brain Res. 177, 61–69 (2007).

    Article  CAS  PubMed  Google Scholar 

  35. Rogers, L. J. Light experience and asymmetry of brain function in chickens. Nature 297, 223–225 (1982).

    Article  CAS  PubMed  Google Scholar 

  36. Koshiba, M., Kikuchi, T., Yohda, M. & Nakamura, S. Inversion of the anatomical lateralization of chick thalamofugal visual pathway by light experience. Neurosci. Lett. 318, 113–116 (2002).

    Article  CAS  PubMed  Google Scholar 

  37. Rogers, L. J. Light input and the reversal of functional lateralization in the chicken brain. Behav. Brain Res. 38, 211–221 (1990).

    Article  CAS  PubMed  Google Scholar 

  38. Rogers, L. J. & Deng, C. Corticosterone treatment of the chick embryo affects light-stimulated development of the thalamofugal visual pathway. Behav. Brain Res. 159, 63–71 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Rogers, L. J. & Rajendra, S. Modulation of the development of light-initiated asymmetry in chick thalamofugal visual projections by oestradiol. Exp. Brain Res. 93, 89–94 (1993).

    Article  CAS  PubMed  Google Scholar 

  40. Schwarz, I. M. & Rogers, L. J. Testosterone: a role in the development of brain asymmetry in the chick. Neurosci. Lett. 146, 167–170 (1992).

    Article  CAS  PubMed  Google Scholar 

  41. Rogers, L. J. & Workman, L. Light exposure during incubation affects competitive behaviour in domestic chicks. Appl. Anim. Behav. Sci. 23, 187–198 (1989).

    Article  Google Scholar 

  42. Rogers, L. J. Development and function of lateralization in the avian brain. Brain Res. Bull. 76, 235–244 (2008).

    Article  PubMed  Google Scholar 

  43. Schaafsma, S. M., Riedstra, B. J., Pfannkuche, K. A., Bouma, A. & Groothuis, T. G. Epigenesis of behavioural lateralization in humans and other animals. Phil. Trans. R. Soc. B 364, 915–927 (2009).

    Article  CAS  PubMed  Google Scholar 

  44. Gunturkun, O. et al. Asymmetry pays: visual lateralization improves discrimination success in pigeons. Curr. Biol. 10, 1079–1081 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Manns, M. & Gunturkun, O. Light experience induces differential asymmetry pattern of GABA- and parvalbumin-positive cells in the pigeon's visual midbrain. J. Chem. Neuroanat. 25, 249–259 (2003).

    Article  CAS  PubMed  Google Scholar 

  46. Manns, M. & Gunturkun, O. Monocular deprivation alters the direction of functional and morphological asymmetries in the pigeon's (Columba livia) visual system. Behav. Neurosci. 113, 1257–1266 (1999).

    Article  CAS  PubMed  Google Scholar 

  47. Gunturkun, O. Morphological asymmetries of the tectum opticum in the pigeon. Exp. Brain Res. 116, 561–566 (1997).

    Article  CAS  PubMed  Google Scholar 

  48. Gunturkun, O., Hellmann, B., Melsbach, G. & Prior, H. Asymmetries of representation in the visual system of pigeons. Neuroreport 9, 4127–4130 (1998).

    Article  CAS  PubMed  Google Scholar 

  49. Gunturkun, B. in The Asymmetrical Brain (eds Hugdahl, K. & Davidson, R. J.) 3–36 (MIT Press, 2003).

    Google Scholar 

  50. Keysers, C., Diekamp, B. & Gunturkun, B. Evidence for physiological asymmetries in the intertectal connections of the pigeon (Columba livia) and their potential role in brain lateralisation. Brain Res. 852, 406–413 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Gunturkun, B. How asymmetry in animals starts. Eur. Rev. 13, 105–118 (2005).

    Article  Google Scholar 

  52. Verhaal, J., Kirsch, J. A., Vlachos, I., Manns, M. & Gunturkun, O. Lateralized reward-related visual discrimination in the avian entopallium. Eur. J. Neurosci. 35, 1337–1343 (2012).

    Article  PubMed  Google Scholar 

  53. Concha, M. L., Signore, I. A. & Colombo, A. Mechanisms of directional asymmetry in the zebrafish epithalamus. Semin. Cell Dev. Biol. 20, 498–509 (2009).

    Article  PubMed  Google Scholar 

  54. Concha, M. L. & Wilson, S. W. Asymmetry in the epithalamus of vertebrates. J. Anat. 199, 63–84 (2001).

    Article  CAS  PubMed  Google Scholar 

  55. Concha, M. L., Burdine, R. D., Russell, C., Schier, A. F. & Wilson, S. W. A nodal signaling pathway regulates the laterality of neuroanatomical asymmetries in the zebrafish forebrain. Neuron 28, 399–409 (2000). This paper provides direct evidence that the development of nervous system asymmetry in vertebrates is linked to asymmetric gene expression in the brain. It also shows that independent genetic mechanisms control the development of structural asymmetries and their directionality (left or right).

    Article  CAS  PubMed  Google Scholar 

  56. Regan, J. C., Concha, M. L., Roussigne, M., Russell, C. & Wilson, S. W. An Fgf8-dependent bistable cell migratory event establishes CNS asymmetry. Neuron 61, 27–34 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Concha, M. L. et al. Local tissue interactions across the dorsal midline of the forebrain establish CNS laterality. Neuron 39, 423–438 (2003).

    Article  CAS  PubMed  Google Scholar 

  58. Bianco, I. H., Carl, M., Russell, C., Clarke, J. D. & Wilson, S. W. Brain asymmetry is encoded at the level of axon terminal morphology. Neural Dev. 3, 9 (2008). This study builds on results in references 61 and 62 to identify two subtypes of habenular projection neuron that are present in different ratios on the left and right and innervate different, non-overlapping regions of their target nucleus with morphologically distinct terminal arbors.

    Article  PubMed Central  PubMed  Google Scholar 

  59. Gamse, J. T., Thisse, C., Thisse, B. & Halpern, M. E. The parapineal mediates left-right asymmetry in the zebrafish diencephalon. Development 130, 1059–1068 (2003).

    Article  CAS  PubMed  Google Scholar 

  60. Aizawa, H., Amo, R. & Okamoto, H. Phylogeny and ontogeny of the habenular structure. Front. Neurosci. 5, 138 (2011).

    Article  PubMed Central  PubMed  Google Scholar 

  61. Aizawa, H. et al. Laterotopic representation of left-right information onto the dorso-ventral axis of a zebrafish midbrain target nucleus. Curr. Biol. 15, 238–243 (2005).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Gamse, J. T. et al. Directional asymmetry of the zebrafish epithalamus guides dorsoventral innervation of the midbrain target. Development 132, 4869–4881 (2005).

    Article  CAS  PubMed  Google Scholar 

  63. Agetsuma, M. et al. The habenula is crucial for experience-dependent modification of fear responses in zebrafish. Nature Neurosci. 13, 1354–1356 (2010).

    Article  CAS  PubMed  Google Scholar 

  64. Aizawa, H., Goto, M., Sato, T. & Okamoto, H. Temporally regulated asymmetric neurogenesis causes left-right difference in the zebrafish habenular structures. Dev. Cell 12, 87–98 (2007). This paper shows that left–right differences in the time of neurogenesis underlie the development of cell-type asymmetries in the zebrafish brain.

    Article  CAS  PubMed  Google Scholar 

  65. Roussigne, M., Bianco, I. H., Wilson, S. W. & Blader, P. Nodal signalling imposes left-right asymmetry upon neurogenesis in the habenular nuclei. Development 136, 1549–1557 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Lee, A. et al. The habenula prevents helpless behavior in larval zebrafish. Curr. Biol. 20, 2211–2216 (2010).

    Article  CAS  PubMed  Google Scholar 

  67. Amat, J. et al. The role of the habenular complex in the elevation of dorsal raphe nucleus serotonin and the changes in the behavioral responses produced by uncontrollable stress. Brain Res. 917, 118–126 (2001).

    Article  CAS  PubMed  Google Scholar 

  68. Stensmyr, M. C. & Maderspacher, F. Pheromones: fish fear factor. Curr. Biol. 22, R183–R186 (2012).

    Article  CAS  PubMed  Google Scholar 

  69. Hendricks, M. & Jesuthasan, S. Asymmetric innervation of the habenula in zebrafish. J. Comp. Neurol. 502, 611–619 (2007).

    Article  PubMed  Google Scholar 

  70. Miyasaka, N. et al. From the olfactory bulb to higher brain centers: genetic visualization of secondary olfactory pathways in zebrafish. J. Neurosci. 29, 4756–4767 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Okamoto, H., Agetsuma, M. & Aizawa, H. Genetic dissection of the zebrafish habenula, a possible switching board for selection of behavioral strategy to cope with fear and anxiety. Dev. Neurobiol. 72, 386–394 (2012).

    Article  PubMed  Google Scholar 

  72. Barth, K. A. et al. fsi zebrafish show concordant reversal of laterality of viscera, neuroanatomy, and a subset of behavioral responses. Curr. Biol. 15, 844–850 (2005).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Dadda, M., Domenichini, A., Piffer, L., Argenton, F. & Bisazza, A. Early differences in epithalamic left-right asymmetry influence lateralization and personality of adult zebrafish. Behav. Brain Res. 206, 208–215 (2010).

    Article  PubMed  Google Scholar 

  74. Facchin, L., Burgess, H. A., Siddiqi, M., Granato, M. & Halpern, M. E. Determining the function of zebrafish epithalamic asymmetry. Phil. Trans. R. Soc. B. 364, 1021–1032 (2009).

    Article  CAS  PubMed  Google Scholar 

  75. Gutierrez-Ibanez, C., Reddon, A. R., Kreuzer, M. B., Wylie, D. R. & Hurd, P. L. Variation in asymmetry of the habenular nucleus correlates with behavioural asymmetry in a cichlid fish. Behav. Brain Res. 221, 189–196 (2011).

    Article  PubMed  Google Scholar 

  76. Reddon, A. R., Gutierrez-Ibanez, C., Wylie, D. R. & Hurd, P. L. The relationship between growth, brain asymmetry and behavioural lateralization in a cichlid fish. Behav. Brain Res. 201, 223–228 (2009).

    Article  PubMed  Google Scholar 

  77. Andrew, R. J., Osorio, D. & Budaev, S. Light during embryonic development modulates patterns of lateralization strongly and similarly in both zebrafish and chick. Phil. Trans. R. Soc. B. 364, 983–989 (2009).

    Article  CAS  PubMed  Google Scholar 

  78. de Borsetti, N. H. et al. Light and melatonin schedule neuronal differentiation in the habenular nuclei. Dev. Biol. 358, 251–261 (2011).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Andrew, R. J., Johnston, A. N., Robins, A. & Rogers, L. J. Light experience and the development of behavioural lateralisation in chicks. II. Choice of familiar versus unfamiliar model social partner. Behav. Brain Res. 155, 67–76 (2004).

    Article  PubMed  Google Scholar 

  80. Pierce-Shimomura, J. T., Faumont, S., Gaston, M. R., Pearson, B. J. & Lockery, S. R. The homeobox gene lim-6 is required for distinct chemosensory representations in C. elegans. Nature 410, 694–698 (2001).

    Article  CAS  PubMed  Google Scholar 

  81. Goldsmith, A. D., Sarin, S., Lockery, S. & Hobert, O. Developmental control of lateralized neuron size in the nematode Caenorhabditis elegans. Neural Dev. 5, 33 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Yu, S., Avery, L., Baude, E. & Garbers, D. L. Guanylyl cyclase expression in specific sensory neurons: a new family of chemosensory receptors. Proc. Natl Acad. Sci. USA 94, 3384–3387 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Poole, R. J., Bashllari, E., Cochella, L., Flowers, E. B. & Hobert, O. A. Genome-wide RNAi screen for factors involved in neuronal specification in Caenorhabditis elegans. PLoS Genet. 7, e1002109 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Miller, A. C., Thiele, T. R., Faumont, S., Moravec, M. L. & Lockery, S. R. Step-response analysis of chemotaxis in Caenorhabditis elegans. J. Neurosci. 25, 3369–3378 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Dusenbery, D. B. Responses of the nematode Caenorhabditis elegans to controlled chemical stimulation. J. Comp. Physiol. 136, 327–331 (1980).

    Article  Google Scholar 

  86. Suzuki, H. et al. Functional asymmetry in Caenorhabditis elegans taste neurons and its computational role in chemotaxis. Nature 454, 114–117 (2008). This paper uses direct functional evidence from C. elegans to show how a simple asymmetric circuit design can process sensory inputs (salt concentration) to guide distinct chemotactic behaviours that reflect the changes in salt concentration experienced by the animal.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Vallortigara, G. & Rogers, L. J. Survival with an asymmetrical brain: advantages and disadvantages of cerebral lateralization. Behav. Brain Sci. 28, 575–589; discussion 589–633 (2005).

    PubMed  Google Scholar 

  88. Vallortigara, G. The evolutionary psychology of left and right: costs and benefits of lateralization. Dev. Psychobiol. 48, 418–427 (2006).

    Article  PubMed  Google Scholar 

  89. Levy, J. The mammalian brain and the adaptive advantage of cerebral asymmetry. Ann. NY Acad. Sci. 299, 264–272 (1977).

    Article  CAS  PubMed  Google Scholar 

  90. Ringo, J. L., Doty, R. W., Demeter, S. & Simard, P. Y. Time is of the essence: a conjecture that hemispheric specialization arises from interhemispheric conduction delay. Cereb. Cortex 4, 331–343 (1994).

    Article  CAS  PubMed  Google Scholar 

  91. Rogers, L. J., Zucca, P. & Vallortigara, G. Advantages of having a lateralized brain. Proc. Biol. Sci. 271, S420–S422 (2004). This paper and reference 44 provide evidence that brain lateralization in birds is associated with an enhanced ability to perform tasks with ecological relevance. It also shows that lateralization is involved in parallel processing, as lateralization correlates with an enhanced ability to perform two simultaneous tasks: finding food and being vigilant for predators.

    Article  PubMed Central  PubMed  Google Scholar 

  92. Manns, M. & Romling, J. The impact of asymmetrical light input on cerebral hemispheric specialization and interhemispheric cooperation. Nature Commun. 3, 696 (2012).

    Article  CAS  Google Scholar 

  93. Sun, Y. F., Lee, J. S. & Kirby, R. Brain imaging findings in dyslexia. Pediatr. Neonatol. 51, 89–96 (2010).

    Article  PubMed  Google Scholar 

  94. Leonard, C. M. & Eckert, M. A. Asymmetry and dyslexia. Dev. Neuropsychol. 33, 663–681 (2008).

    Article  PubMed Central  PubMed  Google Scholar 

  95. Oertel-Knochel, V. & Linden, D. E. Cerebral asymmetry in schizophrenia. Neuroscientist 17, 456–467 (2011).

    Article  PubMed  Google Scholar 

  96. Toth, C., Rajput, M. & Rajput, A. H. Anomalies of asymmetry of clinical signs in parkinsonism. Mov. Disord. 19, 151–157 (2004).

    Article  PubMed  Google Scholar 

  97. Garcia-Toro, M., Montes, J. M. & Talavera, J. A. Functional cerebral asymmetry in affective disorders: new facts contributed by transcranial magnetic stimulation. J. Affect. Disord. 66, 103–109 (2001).

    Article  CAS  PubMed  Google Scholar 

  98. Dadda, M., Zandona, E., Agrillo, C. & Bisazza, A. The costs of hemispheric specialization in a fish. Proc. Biol. Sci. 276, 4399–4407 (2009).

    Article  PubMed Central  PubMed  Google Scholar 

  99. Sulston, J. E., Schierenberg, E., White, J. G. & Thomson, J. N. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev. Biol. 100, 64–119 (1983).

    Article  CAS  PubMed  Google Scholar 

  100. Wes, P. D. & Bargmann, C. I. C. elegans odour discrimination requires asymmetric diversity in olfactory neurons. Nature 410, 698–701 (2001). This paper shows that asymmetries in sensory neurons allow the discrimination of odours in C. elegans.

    Article  CAS  PubMed  Google Scholar 

  101. Thulborn, K. R., Carpenter, P. A. & Just, M. A. Plasticity of language-related brain function during recovery from stroke. Stroke 30, 749–754 (1999).

    Article  CAS  PubMed  Google Scholar 

  102. Saur, D. et al. Dynamics of language reorganization after stroke. Brain 129, 1371–1384 (2006).

    Article  PubMed  Google Scholar 

  103. Heiss, W. D. & Thiel, A. A proposed regional hierarchy in recovery of post-stroke aphasia. Brain Lang. 98, 118–123 (2006).

    Article  PubMed  Google Scholar 

  104. Signore, I. A. et al. Zebrafish and medaka: model organisms for a comparative developmental approach of brain asymmetry. Phil. Trans. R. Soc. B 364, 991–1003 (2009).

    Article  PubMed  Google Scholar 

  105. Villalon, A. et al. Evolutionary plasticity of habenular asymmetry with a conserved efferent connectivity pattern. PLoS ONE 7, e35329 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  106. Hori, M. Frequency-dependent natural selection in the handedness of scale-eating cichlid fish. Science 260, 216–219 (1993).

    Article  CAS  PubMed  Google Scholar 

  107. Palmer, A. R. Scale-eating cichlids: from hand(ed) to mouth. J. Biol. 9, 11 (2010).

    Article  PubMed Central  PubMed  Google Scholar 

  108. Stewart, T. A. & Albertson, R. C. Evolution of a unique predatory feeding apparatus: functional anatomy, development and a genetic locus for jaw laterality in Lake Tanganyika scale-eating cichlids. BMC Biol. 8, 8 (2010).

    Article  PubMed Central  PubMed  Google Scholar 

  109. Van Dooren, T. J., van Goor, H. A. & van Putten, M. Handedness and asymmetry in scale-eating cichlids: antisymmetries of different strength. Evolution 64, 2159–2165 (2010).

    PubMed  Google Scholar 

  110. Bardin, J. Neuroscience: making connections. Nature 483, 394–396 (2012).

    Article  CAS  PubMed  Google Scholar 

  111. Denk, W., Briggman, K. L. & Helmstaedter, M. Structural neurobiology: missing link to a mechanistic understanding of neural computation. Nature Rev. Neurosci. 13, 351–358 (2012).

    Article  CAS  Google Scholar 

  112. O'Rourke, N. A., Weiler, N. C., Micheva, K. D. & Smith, S. J. Deep molecular diversity of mammalian synapses: why it matters and how to measure it. Nature Rev. Neurosci. 13, 365–379 (2012).

    Article  CAS  Google Scholar 

  113. Weissman, T. A., Sanes, J. R., Lichtman, J. W. & Livet, J. Generating and imaging multicolor Brainbow mice. Cold Spring Harb. Protoc. 2011, 763–769 (2011).

    PubMed  Google Scholar 

  114. Badzakova-Trajkov, G., Haberling, I. S., Roberts, R. P. & Corballis, M. C. Cerebral asymmetries: complementary and independent processes. PLoS ONE 5, e9682 (2010).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  115. Lim, D. H. et al. In vivo large-scale cortical mapping using channelrhodopsin-2 stimulation in transgenic mice reveals asymmetric and reciprocal relationships between cortical areas. Front. Neural Circuits 6, 11 (2012).

    Article  PubMed Central  PubMed  Google Scholar 

  116. Levitan, S. & Reggia, J. A. A computational model of lateralization and asymmetries in cortical maps. Neural Comput. 12, 2037–2062 (2000).

    Article  CAS  PubMed  Google Scholar 

  117. Ocklenburg, S. & Gunturkun, O. Hemispheric asymmetries: the comparative view. Front. Psychol. 3, 5 (2012).

    Article  PubMed Central  PubMed  Google Scholar 

  118. Denenberg, V. H., Garbanati, J., Sherman, D. A., Yutzey, D. A. & Kaplan, R. Infantile stimulation induces brain lateralization in rats. Science 201, 1150–1152 (1978).

    Article  CAS  PubMed  Google Scholar 

  119. Verstynen, T., Tierney, R., Urbanski, T. & Tang, A. Neonatal novelty exposure modulates hippocampal volumetric asymmetry in the rat. Neuroreport 12, 3019–3022 (2001).

    Article  CAS  PubMed  Google Scholar 

  120. Tang, A. C., Zou, B., Reeb, B. C. & Connor, J. A. An epigenetic induction of a right-shift in hippocampal asymmetry: selectivity for short- and long-term potentiation but not post-tetanic potentiation. Hippocampus 18, 5–10 (2008).

    Article  PubMed  Google Scholar 

  121. Tang, A. C. & Verstynen, T. Early life environment modulates 'handedness' in rats. Behav. Brain Res. 131, 1–7 (2002).

    Article  PubMed  Google Scholar 

  122. Tang, A. C., Reeb, B. C., Romeo, R. D. & McEwen, B. S. Modification of social memory, hypothalamic-pituitary-adrenal axis, and brain asymmetry by neonatal novelty exposure. J. Neurosci. 23, 8254–8260 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Tang, A. C. & Reeb, B. C. Neonatal novelty exposure, dynamics of brain asymmetry, and social recognition memory. Dev. Psychobiol. 44, 84–93 (2004).

    Article  PubMed  Google Scholar 

  124. Govind, C. K. Claw asymmetry in lobsters: case study in developmental neuroethology. J. Neurobiol. 23, 1423–1445 (1992).

    Article  CAS  PubMed  Google Scholar 

  125. Govind, C. K. & Pearce, J. Differential reflex activity determines claw and closer muscle asymmetry in developing lobsters. Science 233, 354–356 (1986).

    Article  CAS  PubMed  Google Scholar 

  126. Barneoud, P. & Van der Loos, H. Direction of handedness linked to hereditary asymmetry of a sensory system. Proc. Natl Acad. Sci. USA 90, 3246–3250 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Roussigne, M., Blader, P. & Wilson, S. W. Breaking symmetry: the zebrafish as a model for understanding left-right asymmetry in the developing brain. Dev. Neurobiol. 72, 269–281 (2011).

    Article  Google Scholar 

  128. Diamond, M. C., Johnson, R. E., Young, D. & Singh, S. S. Age-related morphologic differences in the rat cerebral cortex and hippocampus: male-female; right-left. Exp. Neurol. 81, 1–13 (1983).

    Article  CAS  PubMed  Google Scholar 

  129. Gurusinghe, C. J. & Ehrlich, D. Sex-dependent structural asymmetry of the medial habenular nucleus of the chicken brain. Cell Tissue Res. 240, 149–152 (1985).

    Article  CAS  PubMed  Google Scholar 

  130. Kemali, M., Guglielmotti, V. & Fiorino, L. The asymmetry of the habenular nuclei of female and male frogs in spring and in winter. Brain Res. 517, 251–255 (1990).

    Article  CAS  PubMed  Google Scholar 

  131. Van Eden, C. G., Uylings, H. B. & Van Pelt, J. Sex-difference and left-right asymmetries in the prefrontal cortex during postnatal development in the rat. Dev. Brain Res. 314, 146–153 (1984).

    Article  CAS  Google Scholar 

  132. Wisniewski, A. B. Sexually-dimorphic patterns of cortical asymmetry, and the role for sex steroid hormones in determining cortical patterns of lateralization. Psychoneuroendocrinology 23, 519–547 (1998).

    Article  CAS  PubMed  Google Scholar 

  133. Amunts, K. et al. Gender-specific left-right asymmetries in human visual cortex. J. Neurosci. 27, 1356–1364 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Luders, E. et al. Hemispheric asymmetries in cortical thickness. Cereb. Cortex 16, 1232–1238 (2006).

    Article  CAS  PubMed  Google Scholar 

  135. Blanton, R. E. et al. Gender differences in the left inferior frontal gyrus in normal children. Neuroimage 22, 626–636 (2004).

    Article  PubMed  Google Scholar 

  136. Rademacher, J., Morosan, P., Schleicher, A., Freund, H. J. & Zilles, K. Human primary auditory cortex in women and men. Neuroreport 12, 1561–1565 (2001).

    Article  CAS  PubMed  Google Scholar 

  137. Huster, R. J., Westerhausen, R., Kreuder, F., Schweiger, E. & Wittling, W. Hemispheric and gender related differences in the midcingulum bundle: a DTI study. Hum. Brain Mapp. 30, 383–391 (2009).

    Article  PubMed  Google Scholar 

  138. Hsu, J. L. et al. Gender differences and age-related white matter changes of the human brain: a diffusion tensor imaging study. Neuroimage 39, 566–577 (2008).

    Article  PubMed  Google Scholar 

  139. Amunts, K., Jancke, L., Mohlberg, H., Steinmetz, H. & Zilles, K. Interhemispheric asymmetry of the human motor cortex related to handedness and gender. Neuropsychologia 38, 304–312 (2000).

    Article  CAS  PubMed  Google Scholar 

  140. Suganthy, J. et al. Gender- and age-related differences in the morphology of the corpus callosum. Clin. Anat. 16, 396–403 (2003).

    Article  CAS  PubMed  Google Scholar 

  141. Kovalev, V. A., Kruggel, F. & von Cramon, D. Y. Gender and age effects in structural brain asymmetry as measured by MRI texture analysis. Neuroimage 19, 895–905 (2003).

    Article  PubMed  Google Scholar 

  142. Kulynych, J. J., Vladar, K., Jones, D. W. & Weinberger, D. R. Gender differences in the normal lateralization of the supratemporal cortex: MRI surface-rendering morphometry of Heschl's gyrus and the planum temporale. Cereb. Cortex 4, 107–118 (1994).

    Article  CAS  PubMed  Google Scholar 

  143. Gurusinghe, C. J., Zappia, J. V. & Ehrlich, D. The influence of testosterone on the sex-dependent structural asymmetry of the medial habenular nucleus in the chicken. J. Comp. Neurol. 253, 153–162 (1986).

    Article  CAS  PubMed  Google Scholar 

  144. Hausmann, M. & Bayer, U. in The Two Halves Of The Brain. Information Processing In The Cerebral Hemispheres (eds Hugdahl, K. & Westerfield, M.) 253–285 (MIT Press, 2010).

    Book  Google Scholar 

  145. Gazzaniga, M. S. Forty-five years of split-brain research and still going strong. Nature Rev. Neurosci. 6, 653–659 (2005).

    Article  CAS  Google Scholar 

  146. Wolman, D. The split brain: a tale of two halves. Nature 483, 260–263 (2012).

    Article  CAS  PubMed  Google Scholar 

  147. Baynes, K., Eliassen, J. C., Lutsep, H. L. & Gazzaniga, M. S. Modular organization of cognitive systems masked by interhemispheric integration. Science 280, 902–905 (1998).

    Article  CAS  PubMed  Google Scholar 

  148. Turk, D. J. et al. Mike or me? Self-recognition in a split-brain patient. Nature Neurosci. 5, 841–842 (2002).

    Article  CAS  PubMed  Google Scholar 

  149. Bianco, I. H. & Wilson, S. W. The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain. Phil. Trans. R. Soc. B 364, 1005–1020 (2009).

    Article  PubMed  Google Scholar 

  150. Poole, R. J. & Hobert, O. Early embryonic programming of neuronal left/right asymmetry in C. elegans. Curr. Biol. 16, 2279–2292 (2006). This paper uncovers the molecular–genetic pathway that generates functional asymmetry between the ASE chemosensory neurons, showing that a Notch-dependent symmetry-breaking event that acts along the anterior–posterior axis early in development results in different genetic programmes being established in the lineages that generate ASEL and ASER.

    Article  CAS  PubMed  Google Scholar 

  151. Sagasti, A. Three ways to make two sides: genetic models of asymmetric nervous system development. Neuron 55, 345–351 (2007).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank members of our laboratories, colleagues, R. Poole and the referees for discussions and comments on the manuscript, and K. Palma for help in drawing the figures. Our work on this topic is supported by the Wellcome Trust (I.H.B. and S.W.W.), the Howard Hughes Medical Institute (M.L.C.), Fondecyt (1090242, 1120558: M.L.C.) and the Millennium Science Initiative (P09-015-F: M.L.C.).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Miguel L. Concha, Isaac H. Bianco or Stephen W. Wilson.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Miguel L. Concha's homepage

Stephen W. Wilson's homepage

Glossary

Bilateria

Animals showing bilateral symmetry: that is, having left and right sides defined by their anterior to posterior (head to tail) and dorsal to ventral (back to front) axes.

Ontogeny

The development of the animal from fertilized egg to maturity.

Thalamofugal

The thalamofugal pathway is a set of central visual pathways in birds that is equivalent to the mammalian geniculocortical pathway.

Tectofugal pathway

A set of central visual pathways in birds that is equivalent to the extrageniculocortical pathway of mammals.

Arcuate fasciculus

A tract linking the language association areas of Broca and Wernicke.

Corpus callosum

The major commissural pathway that connects the left and right hemispheres.

Antisymmetry

Equal frequency of left and right sidedness of the asymmetry within the population.

Directional asymmetry

A predominant sidedness to the asymmetry within the population.

Visual hyperpallium

A region (along with the entopallium) of the bird telencephalon that is involved in visual processing of information from the tectofugal and thalamofugal pathways, respectively.

Precocial

Species in which the young are relatively mature and mobile from the moment of birth or hatching.

Altricial

Species in which the young are highly dependent from the moment of birth or hatching

Functional MRI

Functional MRI detects changes in blood flow that correlate with intensity of neuronal activity, providing a technique for assessing which brain areas are active during particular cognitive or other activities.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Concha, M., Bianco, I. & Wilson, S. Encoding asymmetry within neural circuits. Nat Rev Neurosci 13, 832–843 (2012). https://doi.org/10.1038/nrn3371

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn3371

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing