From Asymmetric Neuroanatomy to Lateralised Behaviour
My interest lies in understanding the functional significance of the observed neuroanatomical asymmetries in the vertebrate CNS, and how these asymmetries are linked to lateralised behaviour. My goal is to establish causal relationships between the lateralisation of the epithamalus, its afferent and efferent projections and animal behaviour using genetic, molecular and laser-ablation approaches to manipulate lateralised habenular circuitry and subsequently test animals in our behavioural assays.
In humans, neuroanatomical asymmetries are reflected in the specialised functional abilities residing in the left and right brain hemispheres. The importance of these brain asymmetries is underscored by the fact that several neuropathologies such as autism, dyslexia, schizophrenia and Alzheimer's disease are linked to changes in neuroanatomical asymmetries. Lateralised behaviours, such as handedness in humans and eye preference for prey and predator detection in amphibians is widespread throughout the animal kingdom and even found among invertebrates such as c.elegans and Drosophila.
For many years, our lab has been characterising the asymmetries in the epithalamus (for details see The Asymmetric Brain link). The habenular nuclei are part of a highly conserved limbic system circuit involved in modulating a wide variety of behaviours including anxiety, aggression, and sleep and memory formation. Are the epithalamic asymmetries we observe linked to lateralised behaviour? Due to the conserved nature of the limbic system, we believe that the insights gained in the zebrafish will help to understand functional relationships of neuro-circuitry in higher vertebrates.
This project was initiated in collaboration with Richard Andrew's group at the University of Sussex, and we have previously shown that young larval zebrafish show a lateralization of eye preference when viewing a conspecific (for example their own reflection). Interestingly, the orientation of this bias is reversed in fsi (frequent-situs-inversus) mutant fry that show reversal of epithalamic asymmetries. These ‘reversed' fry also show a ‘bolder' and more exploratory behaviour (Barth et al, 2005).
The initial tests focused on young zebrafish larvae (fry) with genetically reversed epithalamic asymmetries (fsi); I have now extended the analysis to fry with other genetically or experimentally altered epithalamic asymmetries, for example fry with more symmetric habenulae and efferent neuronal circuitry.
I aim to closely dissect the circuitry of fry that show either strong or no lateralized behaviours. Such detailed analysis will help us to understand how complex behaviours are formed and how only slight changes in connectivity can affect the behavioural outcome, making some individual animals more bold and others more anxious. The results will contribute to our understanding of behavioural drives, and might help to shed light on behavioural patterns that are seen in Humans.
In addition, new tests are being devised to address other aspects of behaviour such as sleep and memory formation. The lab is currently undertaking an ENU mutagenesis screen for asymmetry/laterality mutants. Some of these fry are viable and will be used for behavioural testing.
(left panel) In Situ Hybridisation of normal and fsi embryos reversals that visceral asymmetries such as heart looping are reversed in fsi embryos; (right panel) brain asymmetries such as the position of the parapineal (pp) are reversed as well
(left panel) Reversal of parapineal position can be visualised in living fsi x tg(foxd3:GFP) transgenic embryos; (right panel) using lipophilic dyes we show that the dorso-ventral segregation of habenular efferent projections is reversed in fsi fry with reversed pp position. (see Barth et al, 2005 for details)
My initial studies were orientated towards molecular biology and early mouse development; for my PhD I analysed a mutation affecting gastrulation in the mouse in Liz Robertson's lab at Columbia University, USA.
I began my post-doctoral career with Steve Wilson quite a few years ago. Over the years my interests morphed from studying early patterning of the neural plate and the forebrain to CNS asymmetry, and finally on to my current incarnation as a behavioural neurobiologist.
|PhD||Dept of Genetics & Development; Columbia University, New York|
|BSc||Freie Universitaet Berlin, Germany|
|Exchange Student & Research Assistant||Vanderbilt University, Nashville, USA|
|PhD Student||Columbia University, New York, USA|
|Research Fellow||King's College London, UK|
|Senior Research Fellow||Current: University College London, UK|
Shanmugalingam,S., Houart,C., Picker,A., Reifers,F., Macdonald,R., Barth,A., Griffin,K., Brand,M., Wilson,S.W. (2000)
Ace/Fgf8 is required for forebrain commissure formation and patterning of the telencephalon.
Kazanskaya,O.V., Severtzova,E.A., Barth,K.A., Ermakova,G.V., Lukyanov,S.A., Benyumov,A.O., Pannese,M., Boncinelli,E., Wilson,S.W., Zaraisky,A.G. (1997)
Anf: a novel class of vertebrate homeobox genes expressed at the anterior end of the main embryonic axis.
Macdonald,R., Xu,Q., Barth,K.A., Mikkola,I., Holder,N., Fjose,A., Krauss,S., Wilson,S.W. (1994)
Regulatory gene expression boundaries demarcate sites of neuronal differentiation in the embryonic zebrafish forebrain.