Dysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice.

Autor:	Peter S; Netherlands Institute for Neuroscience, Amsterdam 1105 CA, Netherlands., Ten Brinke MM; Department of Neuroscience, Erasmus MC, Rotterdam 3000 DR, Netherlands., Stedehouder J; Department of Psychiatry, Erasmus MC, Rotterdam 3000 DR, Netherlands., Reinelt CM; Institute for Anatomy and Cell Biology, Ulm University, Ulm 89081, Germany., Wu B; Department of Neuroscience, Erasmus MC, Rotterdam 3000 DR, Netherlands., Zhou H; Department of Neuroscience, Erasmus MC, Rotterdam 3000 DR, Netherlands., Zhou K; Department of Neuroscience, Erasmus MC, Rotterdam 3000 DR, Netherlands., Boele HJ; Department of Neuroscience, Erasmus MC, Rotterdam 3000 DR, Netherlands., Kushner SA; Department of Psychiatry, Erasmus MC, Rotterdam 3000 DR, Netherlands., Lee MG; Yonsei University College of Medicine, Seoul 120-752, Korea., Schmeisser MJ; Institute for Anatomy and Cell Biology, Ulm University, Ulm 89081, Germany.; Department of Neurology, Ulm University, Ulm 89081, Germany., Boeckers TM; Institute for Anatomy and Cell Biology, Ulm University, Ulm 89081, Germany., Schonewille M; Department of Neuroscience, Erasmus MC, Rotterdam 3000 DR, Netherlands., Hoebeek FE; Department of Neuroscience, Erasmus MC, Rotterdam 3000 DR, Netherlands., De Zeeuw CI; Netherlands Institute for Neuroscience, Amsterdam 1105 CA, Netherlands.; Department of Neuroscience, Erasmus MC, Rotterdam 3000 DR, Netherlands.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2016 Sep 01; Vol. 7, pp. 12627. Date of Electronic Publication: 2016 Sep 01.
DOI:	10.1038/ncomms12627
Abstrakt:	Loss-of-function mutations in the gene encoding the postsynaptic scaffolding protein SHANK2 are a highly penetrant cause of autism spectrum disorders (ASD) involving cerebellum-related motor problems. Recent studies have implicated cerebellar pathology in the aetiology of ASD. Here we evaluate the possibility that cerebellar Purkinje cells (PCs) represent a critical locus of ASD-like pathophysiology in mice lacking Shank2. Absence of Shank2 impairs both PC intrinsic plasticity and induction of long-term potentiation at the parallel fibre to PC synapse. Moreover, inhibitory input onto PCs is significantly enhanced, most prominently in the posterior lobe where simple spike (SS) regularity is most affected. Using PC-specific Shank2 knockouts, we replicate alterations of SS regularity in vivo and establish cerebellar dependence of ASD-like behavioural phenotypes in motor learning and social interaction. These data highlight the importance of Shank2 for PC function, and support a model by which cerebellar pathology is prominent in certain forms of ASD.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu