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Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/61287

Title: Mutation of Semaphorin-6A Disrupts Limbic and Cortical Connectivity and Models Neurodevelopmental Psychopathology
Author: MORRIS, DEREK
GILL, MICHAEL
CORVIN, AIDEN PETER
MITCHELL, KEVIN
Sponsor: 
Name Grant Number
RP/2007/37
RP/2007/207
PD/2007/20
PD/2004/16
09/IN.1/B2614
08/IN1/B1875
07/RFP/GENF327
07/IN.1/B969
07/IN.1/B960
01/F1/B006

Author's Homepage: http://people.tcd.ie/mgill
http://people.tcd.ie/morrisdw
http://people.tcd.ie/acorvin
http://people.tcd.ie/kemitche
Keywords: Neuroscience
schizophrenia
autism
Issue Date: 2011
Citation: Annette E. Rünker, Colm O'Tuathaigh, Mark Dunleavy,Derek W. Morris, Graham E. Little, Aiden P. Corvin,Michael Gill, David C. Henshall, John L. Waddington, Kevin J. Mitchell, Mutation of Semaphorin-6A Disrupts Limbic and Cortical Connectivity and Models Neurodevelopmental Psychopathology, PLoS ONE, 6, 11,, 2011, e26488
Series/Report no.: PLoS ONE
6
11,
Abstract: Psychiatric disorders such as schizophrenia and autism are characterised by cellular disorganisation and dysconnectivity across the brain and can be caused by mutations in genes that control neurodevelopmental processes. To examine how neurodevelopmental defects can affect brain function and behaviour, we have comprehensively investigated the consequences of mutation of one such gene, Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour and physiology in mice. These analyses reveal a spectrum of widespread but subtle anatomical defects in Sema6A mutants, notably in limbic and cortical cellular organisation, lamination and connectivity. These mutants display concomitant alterations in the electroencephalogram and hyper-exploratory behaviour, which are characteristic of models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory. Mice with mutations in Sema6A or the interacting genes may thus represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting, either directly or through reactive mechanisms, in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. The biological data presented here also make these genes plausible candidates to explain human linkage findings for schizophrenia and autism.
Description: PUBLISHED
URI: http://hdl.handle.net/2262/61287
Related links: http://dx.doi.org/10.1371/journal.pone.0026488
Appears in Collections:Psychiatry (Scholarly Publications)

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