How is brain asymmetry established and what is it good for?. (360G-Wellcome-104682_Z_14_Z)

£2,999,988

It is likely that the nervous systems of all bilaterally symmetric animals are left-right (LR) asymmetric with respect to processing of information and control of behavior. However, we know very little about how asymmetries arise in development, how they are encoded in circuits and what their importance is for nervous system function. This project will use developmental, genetic, imaging and behavioural approaches in zebrafish to address these issues. 1) How do equivalent structures on le ft and right sides of the brain become asymmetric? The habenular nuclei of zebrafish are LR asymmetric with respect to gene expression, sub-nuclear organization, activity patterns and connectivity. Consequently, this region of the brain is well-suited for resolving developmental mechanisms that can impart asymmetry. Through study of mutant fish with brain asymmetry phenotypes, we aim to resolve the genetic and cellular mechanisms that establish this conserved brain asymmetry. 2) How does the diversity of lateralized habenular neuronal subtypes arise? Neuroanatomical analyses reveal two habenular neuron sub-types present in different proportions on left and right but functional imaging reveals greater diversity of lateralized neurons. We will identify molecular correlates of functional diversity, explore genetic and environmental influences on the development of functional asymmetry and resolve how asymmetry is manifest in circuit neuroanatomy. 3) What are the consequences on co gnition and behavior if brain asymmetry is disrupted? Genetic and embryological manipulations enable us to generate fish in which the habenulae have double-left or double-right symmetry or reversed laterality. The habenulae modulate motivation, fear and emotive decision-making and we will assess how developmental alterations to lateralization impact upon functional asymmetries, learning and behaviour. Please note that this section, with citations added, is repeated in the uploaded research v ision document to provide continuity.

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Grant Details

Amount Awarded 2999988
Applicant Surname Wilson
Approval Committee Science Interview Panel
Award Date 2014-07-08T00:00:00+00:00
Financial Year 2013/14
Grant Programme: Title Investigator Award in Science
Internal ID 104682/Z/14/Z
Lead Applicant Prof Stephen Wilson
Partnership Value 2999988
Planned Dates: End Date 2022-06-30T00:00:00+00:00
Planned Dates: Start Date 2015-01-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London