Skip to main content
SpringerLink
Log in

Defining the Role of Cerebellar Purkinje Cells in Autism Spectrum Disorders

  • Journal Club
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Understanding the contribution of cerebellar dysfunction to complex neurological diseases such as autism spectrum disorders (ASD) is an ongoing topic of investigation. In a recent paper, Tsai et al. (Nature 488:647–651, 2012) used a powerful combination of conditional mouse genetics, electrophysiology, behavioral tests, and pharmacological manipulations to address the role of Tuberous sclerosis complex 1 (Tsc1) in Purkinje cells and cerebellar function. The authors make the staggering discovery that morphological and electrophysiological defects in Purkinje cells are linked to system-wide ASD-like behavioral deficits. In this journal club, I discuss the major findings of this paper and critically assess the implications of this seminal work.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Kanner L. Autistic disturbances of affective contact. Nerv Child. 1943;2:217–50.

    Google Scholar 

  2. Fournier KA, Hass CJ, Naik SK, Lodha N, Cauraugh JH. Motor coordination in autism spectrum disorders: a synthesis and meta-analysis. J Autism Dev Disord. 2010;40(10):1227–40.

    Article  PubMed  Google Scholar 

  3. Altman J, Bayer SA. Development of the cerebellar system: in relation to its evolution, structure, and functions. New York: CRC; 1996.

    Google Scholar 

  4. Sillitoe RVFY, Watson C. Cerebellum. In: Watson C, editor. PG, Puelles L, editor. The mouse nervous system: Elsevier Inc; 2012. p. 360–97.

    Google Scholar 

  5. Eluvathingal TJ, Behen ME, Chugani HT, Janisse J, Bernardi B, Chakraborty P, et al. Cerebellar lesions in tuberous sclerosis complex: neurobehavioral and neuroimaging correlates. J Child Neurol. 2006;21(10):846–51.

    Article  PubMed  Google Scholar 

  6. Ertan G, Arulrajah S, Tekes A, Jordan L, Huisman TA. Cerebellar abnormality in children and young adults with tuberous sclerosis complex: MR and diffusion weighted imaging findings. J Neuroradiol. 2010;37(4):231–8.

    Article  PubMed  CAS  Google Scholar 

  7. Weber AM, Egelhoff JC, McKellop JM, Franz DN. Autism and the cerebellum: evidence from tuberous sclerosis. J Autism Dev Disord. 2000;30(6):511–7.

    Article  PubMed  CAS  Google Scholar 

  8. Tsai PT, Hull C, Chu Y, Greene-Colozzi E, Sadowski AR, Leech JM, et al. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature. 2012;488(7413):647–51.

    Article  PubMed  CAS  Google Scholar 

  9. Kwiatkowski DJ, Zhang H, Bandura JL, Heiberger KM, Glogauer M, el-Hashemite N, 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. 2002;11(5):525–34.

    Article  PubMed  CAS  Google Scholar 

  10. Barski JJ, Dethleffsen K, Meyer M. Cre recombinase expression in cerebellar Purkinje cells. Genesis. 2000;28(3–4):93–8.

    Article  PubMed  CAS  Google Scholar 

  11. Tavazoie SF, Alvarez VA, Ridenour DA, Kwiatkowski DJ, Sabatini BL. Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2. Nat Neurosci. 2005;8(12):1727–34.

    Article  PubMed  CAS  Google Scholar 

  12. Bauman ML, Kemper TL. Neuroanatomic observations of the brain in autism: a review and future directions. Int J Dev Neurosci. 2005;23(2–3):183–7.

    Article  PubMed  Google Scholar 

  13. Fatemi SH, Aldinger KA, Ashwood P, Bauman ML, Blaha CD, Blatt GJ, et al. Consensus paper: pathological role of the cerebellum in autism. Cerebellum. 2012;11(3):777–807.

    Article  PubMed  Google Scholar 

  14. Sajdel-Sulkowska EM, Xu M, Koibuchi N. Increase in cerebellar neurotrophin-3 and oxidative stress markers in autism. Cerebellum. 2009;8(3):366–72.

    Article  PubMed  CAS  Google Scholar 

  15. Hutsler JJ, Zhang H. Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders. Brain Res. 2010;1309:83–94.

    Article  PubMed  CAS  Google Scholar 

  16. Meikle L, Pollizzi K, Egnor A, Kramvis I, Lane H, Sahin M, et al. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci. 2008;28(21):5422–32.

    Article  PubMed  CAS  Google Scholar 

  17. Meikle L, Talos DM, Onda H, Pollizzi K, Rotenberg A, Sahin M, et al. A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival. J Neurosci. 2007;27(21):5546–58.

    Article  PubMed  CAS  Google Scholar 

  18. Silverman JL, Yang M, Lord C, Crawley JN. Behavioural phenotyping assays for mouse models of autism. Nat Rev Neurosci. 2010;11(7):490–502.

    Article  PubMed  CAS  Google Scholar 

  19. Tsai P, Sahin M. Mechanisms of neurocognitive dysfunction and therapeutic considerations in tuberous sclerosis complex. Curr Opin Neurol. 2011;24(2):106–13.

    Article  PubMed  CAS  Google Scholar 

  20. Ehninger D, Han S, Shilyansky C, Zhou Y, Li W, Kwiatkowski DJ, et al. Reversal of learning deficits in a Tsc2+/− mouse model of tuberous sclerosis. Nat Med. 2008;14(8):843–8.

    Article  PubMed  CAS  Google Scholar 

  21. Reith RM, McKenna J, Wu H, Hashmi SS, Cho SH, Dash PK, et al. Loss of Tsc2 in Purkinje cells is associated with autistic-like behavior in a mouse model of tuberous sclerosis complex. Neurobiol Dis. 2012;51:93–103.

    Article  PubMed  Google Scholar 

  22. Musolino PL, Stoodley CJ, Schmahmann JD. Essential anatomy of the cerebellum and related structures. In: Boltshauser EaS, J., editor. Cerebellar disorders in children. London: McKeith; 2012. p. 456.

Download references

Conflict of interest

The author declares that there is no conflict of interest in the work presented in this manuscript.

Author information

Authors and Affiliations

  1. Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, 10065, USA

    Anamaria Sudarov

Authors
  1. Anamaria Sudarov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anamaria Sudarov.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sudarov, A. Defining the Role of Cerebellar Purkinje Cells in Autism Spectrum Disorders. Cerebellum 12, 950–955 (2013). https://doi.org/10.1007/s12311-013-0490-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-013-0490-y

Keywords

Search

Navigation