Mouse brain<\/h2>\n
Working with mouse models, Asari uses fluorescent proteins to study visual responses to a light stimulus. These proteins \u2013 delivered to the neurons via an injected virus \u2013 make it possible to tell whether a neuron is active or not. If it\u2019s active, it shines.<\/p>\n But we humans are not mouse-brained. Can Asari\u2019s work tell us anything relevant about our own neural function? \u201cI believe so,\u201d he says. \u201cThe organisation of the retinal circuitry is fairly preserved across species, among mammals especially. So we think our basic findings in mice can be applied to humans by understanding the principles underlying neural circuit functions. This is where a computational approach is very useful \u2013 we can try to build a model to generalise the function of the retina across different species.\u201d<\/p>\n Cornelius Gross, Asari\u2019s colleague and fellow group leader at EMBL Rome, is also looking to mice to help unravel some of the mysteries of the human condition. His interest lies in behaviour, and in understanding the subtle differences between individuals in how mice \u2013 and people \u2013 respond to certain stimuli.<\/p>\n \u201cI\u2019ve always been interested in behaviours associated with defence, fear and anxiety \u2013 I want to understand how our neural circuits encode and control these behaviours<\/a>,\u201d says Gross. He\u2019s focusing on the hypothalamus \u2013 an old part of the brain, in evolutionary terms \u2013 which is associated with some fundamental behaviours, including fear.<\/p>\n As it turns out, there\u2019s not just a single fear circuit in the brain that determines how we respond to threatening stimuli. The type <\/em>of threat matters. Gross has studied two fundamental types of fear: fear of predators, and fear as a response to social threats, such as bullying or aggression. \u201cWe found that there are two separate, independent pathways for handling these two types of threat. Even if the final outputs \u2013 the fear responses \u2013 are the same, they\u2019re encoded by two dedicated circuits in the hypothalamus,\u201d he says. This hadn\u2019t been shown before.<\/p>\n Another finding to emerge from Gross\u2019s work is that there\u2019s also an encoding of space, or territory, when it comes to social interactions. Mice are naturally territorial, and it seems that their awareness of being in a safe place versus being in a threatening place is linked to their neuronal activity. \u201cIn other words,\u201d Gross explains, \u201ca place in the brain that was considered to be only social and instinctive suddenly becomes much more sophisticated \u2013 it has a map of your world, of your territory.\u201d<\/p>\n A smaller but no less fascinating part of the work in Gross\u2019s lab focuses on microglia. These are cells that are born not in the brain but in the yolk sac \u2013 a membrane connected to the embryo in early development. They then migrate into the brain, where \u2013 as shown by in vivo <\/em>imaging \u2013 they\u2019re continuously moving around. But what are they doing?<\/p>\n \u201cWe don\u2019t really know,\u201d says Gross. \u201cThis is a field that\u2019s in its infancy.\u201d What he does know is that during the early period of brain development, when most of the neural connectivity is formed, neurons actively send out signals to microglia. \u201cThese microglia have been described as phagocytic: they eat things,\u201d Gross continues. This led him to a hypothesis: the microglia eat synapses \u2013 the connections between neurons \u2013 that need to be removed for some reason.<\/p>\n Gross and his team subsequently discovered that microglia don\u2019t eat synapses. Not exactly. Rather, they seem to \u2018nibble<\/a>\u2019 parts of synapses and neurons. It\u2019s not yet clear what this nibbling does, but it may promote new contacts between neurons. Also unclear is what determines which neurons get nibbled. \u201cWhat\u2019s the \u2018eat me\u2019 signal?\u201d Gross wonders. \u201cThat\u2019s what we want to find out next.\u201d<\/p>\n EMBL Rome is a hub for EMBL\u2019s neurobiology research, but scientists at other EMBL sites are also active in the field. Kyung-Min Noh \u2013 a group leader at EMBL Heidelberg \u2013 broke the mould when she decided to become a scientist, in a family more inclined towards the arts. It\u2019s perhaps unsurprising, then, that it was aesthetics that first lured her into the field of neurobiology. \u201cWhen you look at neurons under the microscope, you can\u2019t but fall in love,\u201d she says. \u201cThey\u2019re beautiful.\u201d<\/p>\n However, Noh \u2013 a group leader at EMBL Heidelberg \u2013 soon began to look beyond the morphology of the neuron, to what was going on in the nucleus while neurological pathways were being developed in the brain. She found there was a link between neurodevelopmental disorders and chromatin \u2013 the mass of DNA and proteins in the cell nucleus, which plays a role in gene expression. \u201cIn the lab, we\u2019re trying to understand how this works mechanistically \u2013 the molecular mechanisms that link genetic mutations and changes in gene expression to changes in the chromatin,\u201d she says.<\/p>\n One aspect of the research carried out in Noh\u2019s lab focuses on mutations in people with autism spectrum disorders<\/a>: \u201cWe know the genetic mutations happen in the chromatin. They\u2019re all under the umbrella of autism spectrum disorders, but individually they\u2019re very different. We\u2019re trying to understand the differences between these individual molecules, which present behaviourally as autism spectrum disorders. What exactly is happening inside the cells?\u201d<\/p>\n To find out, Noh uses the CRISPR gene editing tool to introduce mutations into mouse cells or human induced pluripotent stem (iPS) cells \u2013 cells that are generated from adult cells and can differentiate into many different cell types. She collaborates with fellow Heidelberg group leaders Judith Zaugg and Christoph M\u00fcller, working with Zaugg\u2019s group on genomic sequencing and bioinformatic analysis, and with M\u00fcller\u2019s group to understand the molecular structure of the chromatin-associated protein complex. \u201cThis collaborative effort means that we can apply the state of the art to all aspects of the work,\u201d says Noh.<\/p>\n Andrew McCarthy, a team leader at EMBL Grenoble, is also interested in molecular structures in the context of neurobiology. Specifically, he wants to uncover the underlying mechanism of the Slit and Roundabout (Slit\u2013Robo)<\/a> cell signalling pathway \u2013 essentially, how signals from outside a cell are transmitted to the inside. \u201cThese are two proteins. Slit is secreted by specialised glial cells in the nervous system, and Robo is the cognate receptor in the neuronal cell membrane. They interact with each other \u2013 they \u2018talk\u2019 to each other \u2013 and we\u2019re trying to figure out how they signal once they interact,\u201d McCarthy says.<\/p>\n These proteins are expressed in the early stages of embryonic development, when the neural networks are being laid down \u2013 connecting the eyes and the muscles to the brain, for example, for the visual and motor systems. \u201cA lot of these developmental processes are very dynamic,\u201d says McCarthy, \u201cso the proteins are sensing their environment rapidly, and cells infer how to grow or retract in different areas.\u201d<\/p>\n Many cancers and other diseases have been linked to these developmental proteins. \u201cNot just Slit and Roundabout,\u201d McCarthy adds. \u201cThere\u2019s a whole plethora of them.\u201d The link is particularly strong in the case of metastatic cancer cells because such proteins can inform cells to migrate and react to their environment. If unregulated, the proteins can induce primary tumour cells to break away and move to other parts of the body.<\/p>\n These are difficult proteins to work with in the lab. \u201cThey\u2019re large, very flexible, and hard to handle,\u201d says McCarthy. But technological developments are making things easier. Improvements in the beamlines at the European Synchrotron Radiation Facility (ESRF), with which EMBL Grenoble has close ties, mean that data can be collected faster, and from smaller crystals. McCarthy would also like to take advantage of developments in electron and light microscopy. \u201cWe know what these proteins look like \u2013 roughly. Now we need to see them in context, moving to or from the cell surface.\u201d<\/p>\n With these scientists following their curiosity down diverse lines of inquiry, our knowledge about the most complex system in the human body is ever increasing. Yet there remains a great mystery to be solved: how did neurons and nervous systems evolve<\/a>? This is the question that intrigues EMBL Heidelberg group leader Detlev Arendt.<\/p>\n \u201cHumans have always wanted to know where we come from, and this is what we\u2019d like to find out,\u201d Arendt says. \u201cWe want to trace evolutionary paths towards neurons and nervous systems. So we look at animals that are more remote on the animal tree \u2013 animals with simple versions of a nervous system, or those that don\u2019t have a nervous system because they branched off earlier.\u201d<\/p>\n![\"Anastasia](\"https:\/\/news.embl.de\/wp-content\/uploads\/2019\/11\/Anastasia-Vlasiuk.jpg\")
Threat and response<\/h2>\n
Eat me<\/h2>\n
![\"Microscopy](\"https:\/\/news.embl.de\/wp-content\/uploads\/2019\/11\/Filopodia.jpg\")
Beneath the surface<\/h2>\n
On individuality<\/h2>\n
![\"Human](\"https:\/\/news.embl.de\/wp-content\/uploads\/2019\/11\/Noh.jpg\")
How proteins signal<\/h2>\n
![\"Slit](\"https:\/\/news.embl.de\/wp-content\/uploads\/2019\/11\/McCarthy2.jpg\")
Origin and evolution<\/h2>\n
Looking to the ocean for answers<\/h2>\n
![\"Neuroid](\"https:\/\/news.embl.de\/wp-content\/uploads\/2019\/11\/Arendt-image-2.jpg\")