̽��ֱ�� of Cambridge - Marta Zlatic

First wiring map of insect brain complete

jg533 — Fri, 10 Mar 2023 08:49:27 +0000

This will help scientists to understand the basic principles by which signals travel through the brain at the neural level and lead to behaviour and learning.

An organism's nervous system, including the brain, is made up of neurons that are connected to each other via synapses. Information in the form of chemicals passes from one neuron to another through these contact points.

̽��ֱ��map of the 3016 neurons that make up the larva of the fruit fly Drosophila melanogaster’s brain, and the detailed circuitry of neural pathways within it, is known as a ‘connectome’.

This is the largest complete brain connectome ever to have been mapped. It is a huge advance on previous work to map very simple brain structures including the roundworm C. elegans, which only has several hundred neurons.

Imaging entire brains has until recently been extremely challenging. Now, technological advances allow scientists to image the entire brain of the fruit fly larvae relatively quickly using electron microscopy, and reconstruct the brain circuits from the resulting data.

̽��ֱ��fruit fly larva has similar brain structures to the adult fruit fly and larger insects, and has a rich behavioural repertoire, including learning and action-selection.

“ ̽��ֱ��way the brain circuit is structured influences the computations the brain can do. But, up until this point, we haven’t seen the structure of any brain except in very simple organisms,” said Professor Marta Zlatic at the ̽��ֱ�� of Cambridge’s Department of Zoology and the Medical Research Council Laboratory of Molecular Biology (MRC LMB).

Zlatic led the research together with Professor Albert Cardona at the ̽��ֱ�� of Cambridge’s Department of Physiology, Development and Neuroscience and the MRC LMB, and Dr Michael Winding at the ̽��ֱ�� of Cambridge’s Department of Zoology. ̽��ֱ��study, which also involved collaborators from both the UK and the US, is published today in the journal Science.

She added: “Until now, the actual circuit patterns involved in most brain computations have been unknown. Now we can start gaining a mechanistic understanding of how the brain works.”

Current technology is not yet advanced enough to map the connectome of more complex animals such as large mammals. But because all brains involve networks of interconnected neurons, the researchers say that their new map will be a lasting reference for future studies of brain function in other animals.

“All brains of all species have to perform many complex behaviours: for example they all need to process sensory information, learn, choose food, and navigate their environment. In the same way that genes are conserved across the animal kingdom, I think that the basic circuit patterns that drive these fundamental behaviours will also be conserved,” said Zlatic.

To build a picture of the fruit fly larva connectome, the team used thousands of slices of the larva’s brain imaged with a high-resolution electron microscope, to reconstruct a map of the fly’s brain - and painstakingly annotated the connections between neurons. As well as mapping the 3016 neurons, they mapped an incredible 548,000 synapses.

̽��ֱ��researchers also developed computational tools to identify likely pathways of information flow and different types of circuit patterns in the insect’s brain. They found that some of the structural features are similar to state-of-the-art deep learning architecture.

“ ̽��ֱ��most challenging aspect of this work was understanding and interpreting what we saw. We were faced with a complex neural circuit with lots of structure. In collaboration with Professor Priebe and Professor Vogestein’s groups at Johns Hopkins ̽��ֱ��, we developed computational tools to predict the relevant behaviours from the structures. By comparing this biological system, we can potentially also inspire better artificial networks,” said Zlatic.

“This is an exciting and significant body of work by colleagues at the MRC Laboratory of Molecular Biology and others,” said Jo Latimer, Head of Neurosciences and Mental Health at the Medical Research Council.

She added: “Not only have they mapped every single neuron in the insect’s brain, but they’ve also worked out how each neuron is connected. This is a big step forward in addressing key questions about how the brain works, particularly how signals move through the neurons and synapses leading to behaviour, and this detailed understanding may lead to therapeutic interventions in the future.”

̽��ֱ��next step is to delve deeper to understand, for example, the brain circuitry required for specific behavioural functions, such as learning and decision making, and to look at activity in the whole connectome while the insect is doing things.

Adapted from a press release by the Medical Research Council

Reference

Winding, M et al: ‘ ̽��ֱ��connectome of an insect brain.’ Science, 10 March 2023. DOI: 10.1126/science.add9330

Researchers have built the first ever map showing every single neuron and how they’re wired together in the brain of the fruit fly larva.

Now we can start gaining a mechanistic understanding of how the brain works.

Marta Zlatic

Map of the fruit fly brain

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Eight Cambridge researchers elected as members of the European Molecular Biology Organisation

Anonymous — Tue, 07 Jul 2020 13:00:56 +0000

EMBO Membership honours distinguished scientists who have made outstanding contributions to the life sciences, including 88 Nobel Laureates. It is an international organisation of life scientists, which has more than 1800 members elected by peers.

̽��ֱ��newly elected Cambridge researchers are:

Professor Bertie Göttgens, Professor of Molecular Haematology, Deputy Director of the Wellcome MRC Stem Cell Institute, and a member of the Cancer Research UK (CRUK) Cambridge Centre Haematological Malignancies Programme. Bertie’s research group studies how transcription factor networks control the function of blood stem cells, and how mutations that perturb these networks cause leukaemia.

Göttgens said:"This honour is very much a reflection of the dedicated work and collective effort of all members of my research group over the years. Rather fittingly, I kick-started my independent career with a paper in an EMBO Journal. Becoming an EMBO member therefore represents a very special milestone to me."

Professor Kathryn Lilley, Director of the Cambridge Centre for Proteomics, Department of Biochemistry, Milner Therapeutics Institute, and a member of the CRUK Cambridge Centre Cell and Molecular Biology Programme. Kathryn’s research aims to interrogate how the functional proteome correlates with complexity.

Lilley said: “I feel extremely honoured to have been elected as a member of EMBO by my peers, which also recognizes the efforts and achievements on my fabulous research group members and numerous collaborators both past and present.”

Dr Serena Nik-Zainal, a CRUK Advanced Clinician Scientist at the ̽��ֱ��’s MRC Cancer Unit, and Honorary Consultant in Clinical Genetics at Addenbrooke’s Hospital. Serena’s research combines computational and experimental approaches to understand cellular changes and mutational processes that lead to cancer and age-related disorders.

Nik-Zainal said: “It’s a great honour to become a member of EMBO, opening up opportunities for exploring new interactions with colleagues through Europe and around the world.”

Professor Giles Oldroyd FRS, Russell R Geiger Professor of Crop Science at the Sainsbury Laboratory and Director of the Crop Science Centre. Giles is leading an international programme of research that attempts to achieve more equitable and sustainable agriculture through the enhanced use of beneficial microbial associations.

Oldroyd said: “I have long admired the work that EMBO does to strengthen and coordinate science across Europe and it is an honour to now be a part of this prestigious European fellowship of biologists.”

Professor Uta Paszkowski, Professor of Plant Molecular Genetics at the Department of Plant Sciences. Uta leads the Cereal Symbiosis Group, which investigates the molecular mechanisms underlying formation and functioning of arbuscular mycorrhizal symbioses (beneficial interactions between roots of land plants and soil fungi) in rice and maize.

Paszkowski said: “Across the organisations supporting the Life Sciences, EMBO stands out by its varied activities to advance science through facilitating knowledge exchange and career development. I am immensely honoured to be elected as a member.”

Professor Anna Philpott, Head of the School of Biological Sciences, Professor of Cancer and Developmental Biology, and member of the CRUK Cambridge Centre Paediatric Cancer Programme. Anna’s research group at the Wellcome-MRC Cambridge Stem Cell Institute studies the balance between proliferation and differentiation during development and cancer, using a range of models.

Philpott said: “I am delighted to be invited to join an organisation that has done so much for European science.”

Dr Chris Tate, research leader at the MRC Laboratory of Molecular Biology. ̽��ֱ��research in Chris’ lab focusses on understanding the structure and function of the major cell-surface receptors in humans that are targeted by 34% of marketed small molecule drugs.

Tate said: “ ̽��ֱ��election to EMBO Membership is a great honour and will enhance my interactions with the superb scientists throughout Europe. ̽��ֱ��strength of the scientific community in Europe is amazing and we all benefit enormously from being a member of this family.”

Dr Marta Zlatic, research leader at the MRC Laboratory of Molecular Biology. Marta’s lab combines connectomics with physiology and behavioural analysis, in the tractable Drosophila larval model system, to discover the fundamental principles by which brains generate behaviour.

Zlatic said: "I feel extremely honoured and grateful that our research is being recognized in this way."

EMBO Members can actively participate in EMBO’s initiatives by serving on the organisation's Council, committees and editorial boards, participating in the evaluation of applications for EMBO funding, acting as mentors to young scientists in the EMBO community, and advising on key activities. EMBO’s administrative headquarters are in Heidelberg, Germany.

Eight Cambridge researchers - six from the ̽��ֱ�� of Cambridge and two from the MRC Laboratory of Molecular Biology - are among the 63 scientists from around the world elected this year as Members and Associate Members of the European Molecular Biology Organisation (EMBO).

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