'Strikingly similar' brains of man and fly may aid mental health research

(Press-News.org) A new study by scientists at King's College London and the University of Arizona (UA) published in Science reveals the deep similarities in how the brain regulates behaviour in arthropods (such as flies and crabs) and vertebrates (such as fish, mice and humans). The findings shed new light on the evolution of the brain and behaviour and may aid understanding of disease mechanisms underlying mental health problems.

Based on their own findings and available literature, Dr Frank Hirth (King's) and Dr Nicholas Strausfeld (UA) compared the development and function of the central brain regions in arthropods (the 'central complex') and vertebrates (the 'basal ganglia').

Research suggests that both brain structures derive from embryonic stem cells at the base of the developing forebrain and that, despite the major differences between species, their respective constitutions and specifications derive from similar genetic programmes.

The authors describe that nerve cells in the central complex and the basal ganglia become inter-connected and communicate with each other in similar ways, facilitating the regulation of adaptive behaviours. In other words, the response of a fly or a mouse to internal stimuli such as hunger or sleep, and external stimuli such as light/dark or temperature, are regulated by similar neural mechanisms.

Dr Hirth from King's College London Institute of Psychiatry says: "Flies, crabs, mice, humans: all experience hunger, need sleep and have a preference for a comfortable temperature so we speculated there must be a similar mechanism regulating these behaviours. We were amazed to find just how deep the similarities go, despite the differences in size and appearance of these species and their brains."

Dr Strausfeld, a Regents Professor in the UA's Department of Neuroscience and the Director of the UA's Center for Insect Science, says: "When you compare the two structures, you find that they are very similar in terms of how they're organized. Their development is orchestrated by a whole suite of genes that are homologous between flies and mice, and the behavioral deficits resulting from disturbances in the two systems are remarkably similar as well."

In humans, dysfunction of the basal ganglia can cause severe mental health problems ranging from autism, schizophrenia and psychosis, to neurodegeneration - as seen in Parkinson's disease, motor neurone disease and dementia - as well as sleep disturbances, attention deficits and memory impairment. Similarly, when parts of the central complex are affected in fruit flies, they display similar impairments.

Dr Hirth (King's) adds: "The deep similarities we see between how our brains and those of insects regulate behaviour suggest a common evolutionary origin. It means that prototype brain circuits, essential for behavioural choice, originated very early and have been maintained across animal species throughout evolutionary time. As surprising as it may seem, from insects' dysfunctional brains, we can learn a great deal about how human brain disorders come about."

The findings suggest that arthropod and vertebrate brain circuitries derive from a common ancestor already possessing a complex neural structure mediating the selection and maintenance of behavioural actions.

Although no fossil remains of the common ancestor exist, trace fossils, in the form of tracks criss-crossing the seafloor hundreds of millions of years ago, reveal purposeful changes in direction.

Dr Strausfeld (UA) says: "If you compare these tracks to the tracks left behind by a foraging fly larva on an agar plate or the tunnels made by a leaf-mining insect, they’re very similar. They all suggest that the animal chose to perform various different actions, and action selection is precisely what the central complex and the basal ganglia do." The trace fossils may thus support the early existence of brains complex enough to allow for action selection and a shared ancestry of neural structures between invertebrates and vertebrates.

### The study was funded by the UK Medical Research Council (MRC), the Royal Society, Parkinson's UK, Motor Neurone Disease Association, Alzheimer's Research UK, Foundation Thierry Latran (to F.H.), and the Air Force Research Laboratories and the Centre for Insect Science at the University of Arizona (to N.J.S.).

Paper reference: Strausfeld, N.J. and Hirth, F. 'Deep homology of arthropod central complex and vertebrate basal ganglia', Science

For interviews with the authors, please contact: Seil Collins, Press Officer, King's College London, Institute of Psychiatry. Tel: (+44) 0207 848 5377 email: seil.collins@kcl.ac.uk

Nicholas Strausfeld, Department of Neuroscience, The University of Arizona. flybrain@email.arizona.edu

Daniel Stolte, Science Writer, The University of Arizona. Tel: (520) 626-4402 email: stolte@email.arizona.edu

About King's College London: King's College London is one of the top 30 universities in the world (2012/13 QS international world rankings), and was The Sunday Times 'University of the Year 2010/11', and the fourth oldest in England. A research-led university based in the heart of London, King's has more than 25,000 students (of whom more than 10,000 are graduate students) from nearly 140 countries, and more than 6,500 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £525 million (year ending 31 July 2011).

King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar.

King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: http://www.kingshealthpartners.org.

The College is in the midst of a five-year, £500 million fundraising campaign – World questions|King's answers – created to address some of the most pressing challenges facing humanity as quickly as feasible. The campaign's five priority areas are neuroscience and mental health, leadership and society, cancer, global power and children's health. More information about the campaign is available at http://www.kcl.ac.uk/kingsanswers.

About the University of Arizona: Ranked #19 among all public universities in the US by the National Science Foundation, the University of Arizona's mission is to provide a comprehensive, high-quality education that engages its students in discovery through research and broad-based scholarship.

Nobel and Pulitzer Prize winners, members of esteemed national academies and world-renowned experts in dozens of disciplines, UA faculty brings international attention to the University and puts it in the ranks of the top public universities in the US.

The UA generates more than $625 million in research and gives the state an annual $2 billion boost. Strong partnerships with industry turn innovative ideas into thriving enterprises.