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.

Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice

An Author Correction to this article was published on 16 March 2018

This article has been updated

Abstract

Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently reported in autism spectrum disorders (ASD). Although RCrusI is functionally connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to ASD remains unclear. Here neuromodulation of RCrusI in neurotypical humans resulted in altered functional connectivity with the inferior parietal lobule, and children with ASD showed atypical functional connectivity in this circuit. Atypical RCrusI–inferior parietal lobule structural connectivity was also evident in the Purkinje neuron (PN) TscI ASD mouse model. Additionally, chemogenetically mediated inhibition of RCrusI PN activity in mice was sufficient to generate ASD-related social, repetitive, and restricted behaviors, while stimulation of RCrusI PNs rescued social impairment in the PN TscI ASD mouse model. Together, these studies reveal important roles for RCrusI in ASD-related behaviors. Further, the rescue of social behaviors in an ASD mouse model suggests that investigation of the therapeutic potential of cerebellar neuromodulation in ASD may be warranted.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: FC and BOLD activation before and during tDCS administration in neurotypical adults.
Fig. 2: Chemogenetically mediated silencing of RCrusI results in increased activity in left parietal association cortex in mice.
Fig. 3: Altered connectivity between RCrusI and cortical association areas in ASD mouse model and in individuals with ASD.
Fig. 4: Chemogenetically mediated inhibition of RCrusI results in autism-related behaviors in mice.
Fig. 5: Chemogenetically mediated activation of RCrusI rescues social interaction impairment in PN Tsc1-mutant mice.

Change history

  • 16 March 2018

    In the version of this article initially published, the Simons Foundation was missing from the list of sources of support to P.T.T. in the Acknowledgments. The error has been corrected in the HTML and PDF versions of the article.

References

  1. Wingate, M. et al. Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators. Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2010. MMWR Surveill. Summ. 63, 1–21 (2014).

    Google Scholar 

  2. Skefos, J. et al. Regional alterations in purkinje cell density in patients with autism. PLoS One 9, e81255 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Whitney, E. R., Kemper, T. L., Bauman, M. L., Rosene, D. L. & Blatt, G. J. Cerebellar Purkinje cells are reduced in a subpopulation of autistic brains: a stereological experiment using calbindin-D28k. Cerebellum 7, 406–416 (2008).

    Article  PubMed  CAS  Google Scholar 

  4. Limperopoulos, C. et al. Does cerebellar injury in premature infants contribute to the high prevalence of long-term cognitive, learning, and behavioral disability in survivors? Pediatrics 120, 584–593 (2007).

    Article  PubMed  Google Scholar 

  5. Bolduc, M. E. & Limperopoulos, C. Neurodevelopmental outcomes in children with cerebellar malformations: a systematic review. Dev. Med. Child Neurol 51, 256–267 (2009).

    Article  PubMed  Google Scholar 

  6. Catsman-Berrevoets, C. E. & Aarsen, F. K. The spectrum of neurobehavioural deficits in the posterior fossa syndrome in children after cerebellar tumour surgery. Cortex 46, 933–946 (2010).

    Article  PubMed  Google Scholar 

  7. Tsai, P. T. et al. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature 488, 647–651 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. D’Mello, A. M., Crocetti, D., Mostofsky, S. H. & Stoodley, C. J. Cerebellar gray matter and lobular volumes correlate with core autism symptoms. Neuroimage Clin 7, 631–639 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  9. D’Mello, A. M. & Stoodley, C. J. Cerebro-cerebellar circuits in autism spectrum disorder. Front. Neurosci 9, 408 (2015).

    PubMed  PubMed Central  Google Scholar 

  10. Mosconi, M. W., Wang, Z., Schmitt, L. M., Tsai, P. & Sweeney, J. A. The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders. Front. Neurosci 9, 296 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Buckner, R. L., Krienen, F. M., Castellanos, A., Diaz, J. C. & Yeo, B. T. The organization of the human cerebellum estimated by intrinsic functional connectivity. J. Neurophysiol. 106, 2322–2345 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Stoodley, C. J. & Schmahmann, J. D. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex 46, 831–844 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Stoodley, C. J. & Schmahmann, J. D. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. Neuroimage 44, 489–501 (2009).

    Article  PubMed  Google Scholar 

  14. Strick, P. L., Dum, R. P. & Fiez, J. A. Cerebellum and nonmotor function. Annu. Rev. Neurosci. 32, 413–434 (2009).

    Article  PubMed  CAS  Google Scholar 

  15. Grimaldi, G. et al. Cerebellar transcranial direct current stimulation (ctDCS): a novel approach to understanding cerebellar function in health and disease. Neuroscientist 22, 83–97 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  16. De Luca, M., Beckmann, C. F., De Stefano, N., Matthews, P. M. & Smith, S. M. fMRI resting state networks define distinct modes of long-distance interactions in the human brain. Neuroimage 29, 1359–1367 (2006).

    Article  PubMed  Google Scholar 

  17. Deshpande, G., Santhanam, P. & Hu, X. Instantaneous and causal connectivity in resting state brain networks derived from functional MRI data. Neuroimage 54, 1043–1052 (2011).

    Article  PubMed  Google Scholar 

  18. Williams, J. H. et al. Neural mechanisms of imitation and ‘mirror neuron’ functioning in autistic spectrum disorder. Neuropsychologia 44, 610–621 (2006).

    Article  PubMed  Google Scholar 

  19. Clower, D. M., West, R. A., Lynch, J. C. & Strick, P. L. The inferior parietal lobule is the target of output from the superior colliculus, hippocampus, and cerebellum. J. Neurosci. 21, 6283–6291 (2001).

    Article  PubMed  CAS  Google Scholar 

  20. Alexander, G. M. et al. Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors. Neuron 63, 27–39 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Armbruster, B. N., Li, X., Pausch, M. H., Herlitze, S. & Roth, B. L. Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc. Natl. Acad. Sci. USA 104, 5163–5168 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Arancillo, M., White, J. J., Lin, T., Stay, T. L. & Sillitoe, R. V. In vivo analysis of Purkinje cell firing properties during postnatal mouse development. J. Neurophysiol. 113, 578–591 (2015).

    Article  PubMed  Google Scholar 

  23. Peter, S. et al. Dysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice. Nat. Commun. 7, 12627 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Zhou, H. et al. Cerebellar modules operate at different frequencies. eLife 3, e02536 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  25. Khan, A. J. et al. Cerebro-cerebellar resting-state functional connectivity in children and adolescents with autism spectrum disorder. Biol. Psychiatry 78, 625–634 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mesulam, M. M. From sensation to cognition. Brain 121, 1013–1052 (1998).

    Article  PubMed  Google Scholar 

  27. Reep, R. L. & Corwin, J. V. Posterior parietal cortex as part of a neural network for directed attention in rats. Neurobiol. Learn. Mem. 91, 104–113 (2009).

    Article  PubMed  Google Scholar 

  28. Clayden, J. D. Imaging connectivity: MRI and the structural networks of the brain. Funct. Neurol. 28, 197–203 (2013).

    PubMed  PubMed Central  Google Scholar 

  29. Lerch, J. P. et al. Mapping anatomical correlations across cerebral cortex (MACACC) using cortical thickness from MRI. Neuroimage 31, 993–1003 (2006).

    Article  PubMed  Google Scholar 

  30. Asano, E. et al. Autism in tuberous sclerosis complex is related to both cortical and subcortical dysfunction. Neurology 57, 1269–1277 (2001).

    Article  PubMed  CAS  Google Scholar 

  31. Ryu, Y. H. et al. Perfusion impairments in infantile autism on technetium-99m ethyl cysteinate dimer brain single-photon emission tomography: comparison with findings on magnetic resonance imaging. Eur. J. Nucl. Med. 26, 253–259 (1999).

    Article  PubMed  CAS  Google Scholar 

  32. Moy, S. S. et al. Social approach in genetically engineered mouse lines relevant to autism. Genes Brain Behav 8, 129–142 (2009).

    Article  PubMed  CAS  Google Scholar 

  33. Cupolillo, D. et al. Autistic-like traits and cerebellar dysfunction in Purkinje cell PTEN knock-out mice. Neuropsychopharmacology 41, 1457–1466 (2016).

    Article  PubMed  Google Scholar 

  34. Reith, R. M. et al. Loss of Tsc2 in Purkinje cells is associated with autistic-like behavior in a mouse model of tuberous sclerosis complex. Neurobiol. Dis. 51, 93–103 (2013).

    Article  PubMed  CAS  Google Scholar 

  35. Gottlieb, J. From thought to action: the parietal cortex as a bridge between perception, action, and cognition. Neuron 53, 9–16 (2007).

    Article  PubMed  CAS  Google Scholar 

  36. Fogassi, L. et al. Parietal lobe: from action organization to intention understanding. Science 308, 662–667 (2005).

    Article  PubMed  CAS  Google Scholar 

  37. Marko, M. K. et al. Behavioural and neural basis of anomalous motor learning in children with autism. Brain 138, 784–797 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Nebel, M. B. et al. Intrinsic visual-motor synchrony correlates with social deficits in autism. Biol. Psychiatry 79, 633–641 (2016).

    Article  PubMed  Google Scholar 

  39. Haswell, C. C., Izawa, J., Dowell, L. R., Mostofsky, S. H. & Shadmehr, R. Representation of internal models of action in the autistic brain. Nat. Neurosci. 12, 970–972 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Mostofsky, S. H. et al. Developmental dyspraxia is not limited to imitation in children with autism spectrum disorders. J. Int. Neuropsychol. Soc. 12, 314–326 (2006).

    Article  PubMed  Google Scholar 

  41. Stoodley, C. J. & Limperopoulos, C. Structure-function relationships in the developing cerebellum: evidence from early-life cerebellar injury and neurodevelopmental disorders. Semin. Fetal Neonatal Med. 21, 356–364 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Van Overwalle, F., Baetens, K., Mariën, P. & Vandekerckhove, M. Social cognition and the cerebellum: a meta-analysis of over 350 fMRI studies. Neuroimage 86, 554–572 (2014).

    Article  PubMed  Google Scholar 

  43. Jack, A., Englander, Z. A. & Morris, J. P. Subcortical contributions to effective connectivity in brain networks supporting imitation. Neuropsychologia 49, 3689–3698 (2011).

    Article  PubMed  Google Scholar 

  44. Jack, A. & Pelphrey, K. A. Neural correlates of animacy attribution include neocerebellum in healthy adults. Cereb. Cortex 25, 4240–4247 (2015).

    Article  PubMed  Google Scholar 

  45. Deeley, Q. et al. An event related functional magnetic resonance imaging study of facial emotion processing in Asperger syndrome. Biol. Psychiatry 62, 207–217 (2007).

    Article  PubMed  Google Scholar 

  46. LeBlanc, J. J. & Fagiolini, M. Autism: a “critical period” disorder? Neural Plast. 2011, 921680 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Bryant, J. L., Boughter, J. D., Gong, S., LeDoux, M. S. & Heck, D. H. Cerebellar cortical output encodes temporal aspects of rhythmic licking movements and is necessary for normal licking frequency. Eur. J. Neurosci 32, 41–52 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Boggio, P. S., Asthana, M. K., Costa, T. L., Valasek, C. A. & Osório, A. A. Promoting social plasticity in developmental disorders with non-invasive brain stimulation techniques. Front. Neurosci 9, 294 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Demirtas-Tatlidede, A. et al. Safety and proof of principle study of cerebellar vermal theta burst stimulation in refractory schizophrenia. Schizophr. Res. 124, 91–100 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Amadi, U., Ilie, A., Johansen-Berg, H. & Stagg, C. J. Polarity-specific effects of motor transcranial direct current stimulation on fMRI resting state networks. Neuroimage 88, 155–161 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Wechsler, D. Wechsler Intelligence Scale for Children (4th edn.). The Psychological Corporation (San Antonio, Texas, 2003).

    Google Scholar 

  52. Wechsler, D. Wechsler Intelligence Scale for Children (5th edn.). The Psychological Corporation (San Antonio, Texas, 2014).

    Google Scholar 

  53. Whitfield-Gabrieli, S. & Nieto-Castanon, A. Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect 2, 125–141 (2012).

    Article  PubMed  Google Scholar 

  54. Behzadi, Y., Restom, K., Liau, J. & Liu, T. T. A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage 37, 90–101 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Muschelli, J. et al. Reduction of motion-related artifacts in resting state fMRI using aCompCor. Neuroimage 96, 22–35 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Hollingshead, A.B. Four factor index of social status. Yale University Department of Sociology (New Haven, Connecticut, 1975).

  57. Ho, D. E., Imai, K., King, G. & Stuart, E. A. MatchIt: nonparameteric preprocessing for parametric causal inference. J. Stat. Softw. 42, 1–28 (2011).

    Article  Google Scholar 

  58. Stuart, E. A. & Ialongo, N. S. Matching methods for selection of subjects for follow-up. Multivariate Behav. Res. 45, 746–765 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Diedrichsen, J. A spatially unbiased atlas template of the human cerebellum. Neuroimage 33, 127–138 (2006).

    Article  PubMed  Google Scholar 

  60. Diedrichsen, J., Balsters, J. H., Flavell, J., Cussans, E. & Ramnani, N. A probabilistic MR atlas of the human cerebellum. Neuroimage 46, 39–46 (2009).

    Article  PubMed  Google Scholar 

  61. Tzourio-Mazoyer, N. et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15, 273–289 (2002).

    Article  PubMed  CAS  Google Scholar 

  62. Barski, J. J., Dethleffsen, K. & Meyer, M. Cre recombinase expression in cerebellar Purkinje cells. Genesis 28, 93–98 (2000).

    Article  PubMed  CAS  Google Scholar 

  63. Kwiatkowski, D. J. et al. A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. Hum. Mol. Genet 11, 525–534 (2002).

    Article  PubMed  CAS  Google Scholar 

  64. Márquez-Ruiz, J. & Cheron, G. Sensory stimulation-dependent plasticity in the cerebellar cortex of alert mice. PLoS One 7, e36184 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Quiroga, R. Q., Reddy, L., Kreiman, G., Koch, C. & Fried, I. Invariant visual representation by single neurons in the human brain. Nature 435, 1102–1107 (2005).

    Article  PubMed  CAS  Google Scholar 

  66. Quiroga, R. Q., Nadasdy, Z. & Ben-Shaul, Y. Unsupervised spike detection and sorting with wavelets and superparamagnetic clustering. Neural Comput. 16, 1661–1687 (2004).

    Article  PubMed  Google Scholar 

  67. Quiroga, R. Q. Spike sorting. Curr. Biol. 22, R45–R46 (2012).

    Article  PubMed  CAS  Google Scholar 

  68. Bock, N. A., Nieman, B. J., Bishop, J. B. & Mark Henkelman, R. In vivo multiple-mouse MRI at 7 Tesla. Magn. Reson. Med. 54, 1311–1316 (2005).

    Article  PubMed  Google Scholar 

  69. Lerch, J. P. et al. Automated cortical thickness measurements from MRI can accurately separate Alzheimer’s patients from normal elderly controls. Neurobiol. Aging 29, 23–30 (2008).

    Article  PubMed  Google Scholar 

  70. Nieman, B. J., Flenniken, A. M., Adamson, S. L., Henkelman, R. M. & Sled, J. G. Anatomical phenotyping in the brain and skull of a mutant mouse by magnetic resonance imaging and computed tomography. Physiol. Genomics 24, 154–162 (2006).

    Article  PubMed  CAS  Google Scholar 

  71. Dorr, A. E., Lerch, J. P., Spring, S., Kabani, N. & Henkelman, R. M. High resolution three-dimensional brain atlas using an average magnetic resonance image of 40 adult C57Bl/6J mice. Neuroimage 42, 60–69 (2008).

    Article  PubMed  CAS  Google Scholar 

  72. Steadman, P. E. et al. Genetic effects on cerebellar structure across mouse models of autism using a magnetic resonance imaging atlas. Autism Res 7, 124–137 (2014).

    Article  PubMed  Google Scholar 

  73. Ullmann, J. F., Watson, C., Janke, A. L., Kurniawan, N. D. & Reutens, D. C. A segmentation protocol and MRI atlas of the C57BL/6J mouse neocortex. Neuroimage 78, 196–203 (2013).

    Article  PubMed  Google Scholar 

  74. Alexander-Bloch, A., Giedd, J. N. & Bullmore, E. Imaging structural co-variance between human brain regions. Nat. Rev. Neurosci. 14, 322–336 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Bohbot, V. D., Lerch, J., Thorndycraft, B., Iaria, G. & Zijdenbos, A. P. Gray matter differences correlate with spontaneous strategies in a human virtual navigation task. J. Neurosci. 27, 10078–10083 (2007).

    Article  PubMed  CAS  Google Scholar 

  76. Bozzali, M. et al. Anatomical connectivity mapping: a new tool to assess brain disconnection in Alzheimer’s disease. Neuroimage 54, 2045–2051 (2011).

    Article  PubMed  Google Scholar 

  77. Evans, A. C. Networks of anatomical covariance. Neuroimage 80, 489–504 (2013).

    Article  PubMed  CAS  Google Scholar 

  78. Kelly, C. et al. A convergent functional architecture of the insula emerges across imaging modalities. Neuroimage 61, 1129–1142 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Spreng, R. N. & Turner, G. R. Structural covariance of the default network in healthy and pathological aging. J. Neurosci. 33, 15226–15234 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Zielinski, B. A. et al. scMRI reveals large-scale brain network abnormalities in autism. PLoS One 7, e49172 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. The Mouse Nervous System. (eds. Watson C., Paxinos, G. & Peulles, L.) (Academic Press, London, 2011).

    Google Scholar 

  82. Yang, M., Silverman, J.L. & Crawley, J.N. Automated three-chambered social approach task for mice. Curr Protoc. Neurosci. 56, 8.26.1–8.26.16 (2011).

    Google Scholar 

  83. Yuan, E. et al. Graded loss of tuberin in an allelic series of brain models of TSC correlates with survival, and biochemical, histological and behavioral features. Hum. Mol. Genet 21, 4286–4300 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Holmes, A. et al. Behavioral characterization of dopamine D5 receptor null mutant mice. Behav. Neurosci. 115, 1129–1144 (2001).

    Article  PubMed  CAS  Google Scholar 

  85. Silverman, J. L. et al. Sociability and motor functions in Shank1 mutant mice. Brain Res. 1380, 120–137 (2011).

    Article  PubMed  CAS  Google Scholar 

  86. Bednar, I. et al. Selective nicotinic receptor consequences in APP(SWE) transgenic mice. Mol. Cell. Neurosci. 20, 354–365 (2002).

    Article  PubMed  CAS  Google Scholar 

  87. Yang, M. & Crawley, J. N. Simple behavioral assessment of mouse olfaction. Curr. Protoc. Neurosci. 48, 8.24.1–8.24.12 (2009).

    Google Scholar 

  88. Buitrago, M. M., Schulz, J. B., Dichgans, J. & Luft, A. R. Short and long-term motor skill learning in an accelerated rotarod training paradigm. Neurobiol. Learn. Mem. 81, 211–216 (2004).

    Article  PubMed  Google Scholar 

  89. Hayar, A., Bryant, J. L., Boughter, J. D. & Heck, D. H. A low-cost solution to measure mouse licking in an electrophysiological setup with a standard analog-to-digital converter. J. Neurosci. Methods 153, 203–207 (2006).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

A.M.D. and C.J.S. acknowledge the support of P. Turkeltaub, C. Barrett, B. Drury, and S. Martin in neuroimaging data collection and analysis. All neurobehavioral experiments were performed at the Department of Psychiatry Rodent Behavioral Core, and the authors thank the Director for Core services, S. Birnbaum, for her assistance. The authors also appreciate assistance from the UT Southwestern Whole Brain Microscopy Facility, and from B. Nieman and L. Spencer Noakes for their work on the MRI sequence used. P.T.T. acknowledges support from the National Institute of Neurologic Disorders and Stroke of the NIH (K08 NS083733) the Child Neurology Foundation, the Tuberous Sclerosis Alliance, the Simons Foundation, and the University of Texas Southwestern Medical Center Disease Oriented Clinical Scholar Award. C.J.S. acknowledges funding from the National Institute of Mental Health of the NIH (R15 MH106957), pilot research funds from the Department of Psychology, and institutional startup funds from American University. J.P.L. and J.E. acknowledge support from the Canadian Institute for Health Research (CIHR) and the Ontario Brain Institute (OBI). S.H.M. acknowledges support from Autism Speaks, the National Institute of Mental Health (R01 MH085328-09, R01 MH078160-07, and K01 MH109766), and the National Institute of Neurological Disorders and Stroke (R01 NS048527-08). E.K. acknowledges funding from National Institute of Drug Abuse T32 training grant (T32 DA007290-24).

Author information

Authors and Affiliations

Authors

Contributions

C.J.S. and P.T.T. formulated human experiments and analysis, while P.T.T. formulated experiments in mice. P.T.T., J.M.G., F.M., and C.A.C. carried out mouse experiments. A.M.D. and C.J.S. carried out human studies and analysis. J.E. and J.P.L. performed mouse MRI and analysis. C.J.S., A.M.D., M.B.N., and S.H.M. designed the human ASD analysis, and S.H.M. and M.B.N. provided the human ASD data. V.J., P.L., E.K., and J.M.P. performed electrophysiology experiments and analysis. C.J.S., A.M.D., and P.T.T. prepared the manuscript.

Corresponding authors

Correspondence to Catherine J. Stoodley or Peter T. Tsai.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Stoodley, C.J., D’Mello, A.M., Ellegood, J. et al. Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice. Nat Neurosci 20, 1744–1751 (2017). https://doi.org/10.1038/s41593-017-0004-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41593-017-0004-1

Further reading

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