Type

Journal Article

Authors

John L Waddington
David C Henshall
Kevin Mitchell
Graham E Little
Aiden Corvin
Mark Dunleavy
Derek Morris
Colm O'Tuathaigh
Michael Gill
Annette E Rünker

Subjects

Psychiatry

Topics
humans gait locomotion behavior animal female limbic system genetics psychology mice inbred c57bl semaphorin 6a mice neurologic mutants physiopathology male brain function mental disorders mutation memory pathology nerve net social interaction autism life sciences physiology phenotype neuroscience schizophrenia animals disease models animal object recognition anatomical defects anxiety neurodevelopmental psychopathology semaphorins complications prefrontal cortex genes society sema6a protein mouse growth development mice

Mutation of Semaphorin-6A Disrupts Limbic and Cortical Connectivity and Models Neurodevelopmental Psychopathology (2011)

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.
Collections Ireland -> Royal College of Surgeons in Ireland -> Department of Molecular and Cellular Therapeutics
Ireland -> Trinity College Dublin -> RSS Feeds
Ireland -> Royal College of Surgeons in Ireland -> Molecular and Cellular Therapeutics Articles
Ireland -> Trinity College Dublin -> Psychiatry (Scholarly Publications)
Ireland -> Trinity College Dublin -> Psychiatry
Ireland -> Trinity College Dublin -> RSS Feeds
Ireland -> Trinity College Dublin -> School of Medicine

Full list of authors on original publication

John L Waddington, David C Henshall, Kevin Mitchell, Graham E Little, Aiden Corvin, Mark Dunleavy, Derek Morris, Colm O'Tuathaigh, Michael Gill, Annette E Rünker

Experts in our system

1
John L Waddington
Royal College of Surgeons in Ireland
Total Publications: 157
 
2
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 120
 
3
Kevin J Mitchell
Trinity College Dublin
Total Publications: 46
 
4
Graham Little
Trinity College Dublin
Total Publications: 7
 
5
Aiden Corvin
Trinity College Dublin
Total Publications: 190
 
6
Mark Dunleavy
Royal College of Surgeons in Ireland
Total Publications: 19
 
7
Derek Morris
Trinity College Dublin
Total Publications: 150
 
8
Colm M P O'Tuathaigh
Royal College of Surgeons in Ireland
Total Publications: 71
 
9
Michael Gill
Trinity College Dublin
Total Publications: 260