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Professor Marta Zlatic creates first wiring map of insect brain

During the pandemic most of us did a lot less than normal, due to the constraints of lockdowns.

Not so neuroscientist and Trinity Fellow Professor Marta Zlatic, who led a team of scientists in the UK and US to map every neuron in the brain of a fruit fly larva and how they are wired together for the first time.

This gargantuan effort created a 3D map showing all 3016 neurons and their 548,000 connecting synapses in poppy-seed sized brain of the Drosophila melanogaster. This is known as a ‘connectome.’

Professor Marta Zlatic in her laboratory in Cambridge. Photo: MRC Laboratory of Molecular Biology

Step back a few years and Marta Zlatic was studying Natural Sciences after being awarded a Trinity College Eastern European Bursary. She went onto a PhD and then a Junior Research Fellowship at the College.

Professor Zlatic started her own lab at the Howard Hughes Medical Institute (HHMI) Janelia Research Campus, Virginia. Recently she moved back to Cambridge at the invitation of the MRC Laboratory of Molecular Biology (LMB).

Her lab studies the basic principles by which neural circuits generate behaviour. Professor Zlatic has received several awards for her discoveries of circuit mechanisms that underlie learning and decision making, including the Eric Kandel Young Neuroscientist Prize 2017 and the Royal Society Francis Crick Medal 2020.

Her latest achievement, the culmination of five years of research by academics at Cambridge and Johns Hopkins University, is landmark that will enable scientists to understand how the brain processes the flow of sensory information and translates it into action. She said:

Now we have a reference brain connectome. In the future we can look how structure changes when specific memories are written, how structure differs between different individuals that have different behaviours, how it goes awry in models of disease.

The team’s paper, ‘The connectome of an insect brain,’ published in Science on 10 March, received widespread media coverage.

The morphologies of all brain neurons, reconstructed from a synapse-resolution electron microscopy volume (left), and the associated synaptic connectivity map of the entire brain (right). Image: Professor Marta Zlatic / MRC LMB

Imaging brains is challenging – until now only the structure of three simple nervous systems with a few hundred neurons had been mapped (the roundworm C. elegans, the tadpole of a low chordate, and the larva of a marine annelid).

Recent advances in electron microscopy enabled the team to scan thousands of slices of the minute brain of a fruit fly larva. It was painstaking work. But the bigger issue was how to understand what they were looking at and interpret the pathways of information flow and different types of circuitry.

Professor Zlatic and Professor Albert Cardona at Cambridge’s Department of Physiology, Development and Neuroscience, and the MRC LMB, collaborated with Professor Priebe and Professor Vogelstein at Johns Hopkins University, to develop computational tools to predict how structures would behave.

Professor Zlatic explained that current technology is not advanced enough to map the connectome of complex animals such as large mammals. However, she said:

All brains are similar – they are all networks of interconnected neurons – and all brains of all species have to perform many complex behaviours: they all need to process sensory information, learn, select actions, navigate their environments, choose food, recognise their conspecifics, escape from predators etc.

In the same way that genes are conserved across the animal kingdom, I think that the basic circuit motifs that implement these fundamental behaviours will also be conserved.

The team achieved this scientific milestone despite the constraints of the COVID pandemic. ‘Juggling children and research during the pandemic was very hard,’ says Professor Zlatic.

Various people told her what she was aimed to achieve was impossible. ‘You have got to follow your intuition, not be bothered by what other people think. Just get on with your research,’ she said.

Conducting highly complex research and managing a remote team during the pandemic had its stressful moments. Luckily, her main collaborator on the study, Professor Albert Cardona, is her husband so they could get a lot of work done at home.

Marta and Albert met at a conference at HHMI Janelia Research Campus while they were postdocs and started a long-term collaboration. They both secured positions at the institution and ran labs side-by-side for a decade.

In 2019 Cambridge University and MRC LMB invited them back. While both research environments are ‘equally wonderful’, says Professor Zlatic, returning to Cambridge was the right move and closer to family in Croatia and Spain.

I’ve always loved Cambridge, my colleagues, the research; I made a lot of friends. I did my undergraduate degree at Trinity, and there’s that emotional link you develop in your twenties.

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