The Brain Conferences: Cortex Development and Evolution (FENS) – Blog from James Crowe

FENS, The Brain Prize and IBRO-PERC stipend recipient, James Crowe attended The Brain Conferences: Cortex Development and Evolution (FENS), which took place in Copenhagen, Denmark. James is a PhD candidate at the Department of Life and Health Sciences, Aston University, UK. His research focuses upon building human cortical networks-in-a-dish using iPSC-derived neural stem cells, with the aim of exploring network connectivity. James discusses his attendance of the conference where he presented his research.

Attending The Brain Conferences is the highlight of year for any European neuroscientist. These small group high-level meetings are organised by FENS and the Brain Prize on a bi-annual basis to tackle a specific subject matter within neuroscience. Bringing together world-renown neuroscientists allows intense discussions upon current concepts and defining challenges for future research. This year’s Fall conference was on Cortex Evolution and Development.
An international conference can be a daunting prospect if you are a first year PhD student all by yourself, and especially if you are surrounded by the titans of your field whom you idealise. However, it can also be a once-in-a-lifetime opportunity as I found out.

Day one (Sunday): Units of the Cortex

Having spent half a day in Barcelona to recover from my previous conference (no rest for the wicked – or at least PhD students) I found myself soaring across Europe to Copenhagen. The Brain Conference was held in Moltke’s Palæ, a grand mansion in the old town, and a remarkable stage for the following lectures. The first lecture was presented by living legend, Pasko Rakic (Yale University, USA), who first defined the mechanisms involved in cortical development. He discussed his previous work, whereby radioactive tritiated thymidine was introduce to the cortex during embryonic development, and was used to demonstrate the generation of new neurons from radial glial cells, a concept that has allowed us to begin mapping the cortex from the progenitors up to postmitotic neurons.

After a great opening we had a quick coffee break, again a daunting arena for a 1st year PhD student in a sea of accomplished academics. After 5 minutes of nervously staring into my coffee I decided I would make the first move, and was very glad I did so. I met Lorenzo Fabrizi, a research group leader at UCL, London where he studies the effect of somatosensory input on premature babies via fMRI and MEG. I was delighted to hear about his research, and surprised when he was interested in mine. This gave me a real confidence boost and from then on I made many new contacts by being bold and starting conversations.

Following the break, Paul Manger (Wits University, South Africa) gave a great talk upon the evolutionary location of thalamic inputs in cortices with no layer IV neurons are present. Evolution plays a big role in how we believe the brain develops, as the developmental mechanisms gained, lost, or modified, make us uniquely human. Leah Krubritzer (University of California, Davis, USA) spoke after on how sensory deprivation can re-model the function of the cortex itself, which had me furiously taking notes – the plasticity of the cortex amazed me, to think our brains can rewire so efficiently! It was encouraging to see researchers who were very passionate about their work, Paul and Leah both have very hands-on experience which I found inspiring. After the talks we had the opportunity to mingle, and I had the chance to talk face-to-face with the speakers, whose research had both amazed and inspired me.

Day two (Monday): Guessing genes, Observing organoids and Specialised cells

Whilst the first day seemed jam-packed, it had only been a half-day, and the real event was only just starting. Seven hours of lectures and poster presentations lay ahead, and based on the previous days experience I was very excited.

I quickly found I had a right to be. My scientific role model, Madeline Lancaster (University of Cambridge, UK) was attending to present the remarkable story of Organoids and how they model brain development. For those unfamiliar with Organoids, they are effectively 3D “mini-brains” that self-form from mammalian pluripotent stem cells. One of the most exciting ideas about Organoids is that they highlight the ability of our cells to self-create a structure as complicated as the cortex. For me, seeing Madeline speak was the icing-on-the-cake of the conference – I completed my Masters with an encyclopaedic knowledge of her work, and with it being such cutting-edge research I felt lucky to hear about her next endeavour first-hand.

After Madeline’s talk I was delighted to hear about what were affectionally termed “the angels of the cortex”. Cajal-Retzius cells and subplate neurons are often overlooked in cortical studies as they largely transient – but they play a major role in helping to construct the developing cortex. Alessandra Pierani (Institut Jacques Monod, France) and Chiaki Ohtaka-Maruyama described how these cell types guide migrating neurons into the correct position, and how without them, our brains would never properly develop. I am eagerly awaiting the papers that come from their respective labs in the near future, I think it will cause a re-write of neurodevelopmental textbooks.

Before the poster session, Ed Lein (Allen Institute for Brain Sciences, USA) gave us an insight into how to better identify neuronal subtypes. Using a revolutionary new technique known as single nuclei RNAseq, Ed’s lab is able to identify the molecular fingerprint of unique cell types. What was perhaps most interesting was that these weren’t necessarily the same as those previously described by morphological means, hinting that there may be a deeper complexity to the cortex than believed. I look forward to using Ed’s findings to validate my own neuronal models in the lab.

Finally the poster session provided a valuable opportunity to discuss my research with the eminent researchers in the field, and through those discussions I found many new ways of looking at my research. It gave me much food for thought, and even an opportunity to visit new labs to learn techniques I could incorporate into my project.

After a long day of talks, everyone was ready to eat, and we headed for a small dinner at Madklubben Bistro de Luxe. The food was delicious and the conversations deeply interested. I ended up sat next to Ed, and had a great conversation over how his work will affect in vitro research, and potentially teach us about development. I was also sitting opposite Pasko Rakic, and Arnold Kreigstein, which was a real honour, as I listened to their theories and stories with eager ears. By the end of the evening I was sat with Daniel de Toro (Max-Planck-Instutite of Neurobiology) discussing how in the future, big data may help us solve neuroscience conundrums by modelling large scale networks.

Ed Lein and me, apparently too deep in conversation to notice someone was snapping pictures!

Day three (Tuesday): Re-thinking the brain evolution

For the third day, the focus largely switched to evolutionary origins of cell types, numbers and how they form circuits within the brain. It featured talks from Jon Kaas (Vanderbilt University, USA) one of the fathers of modern neuroscience, and Suzana Herculano-Houzel (Vanderbilt University, USA) who has made important distinctions about the fact and myths associated with the number of neurons present in the human brain – and more importantly just what makes our brains special. Furthermore, key talks about avian and reptilian cortices were very captivating – who knew that turtles have a highly developed cortex, or that some birds have more neurons than say, a pig?

To break up the talks, we took a guided tour of Copenhagen, seeing many interesting sights (including the statue of ‘The Little Mermaid’ and a lesser known, but equally impressive statue of Gefjon, a Norse goddess. I absolutely recommend visiting Copenhagen as it is a lovely city, with a lot of culture and good food!

The final talk of the evening was given by co-chair to the talks, Arnold Kriegstein (University of California, USA). Arnold delivered a fascinating talk on his theory of a disconnected radial glial scaffold, changing entirely the way we perceive cortical development. This is all thanks to a discovery made several years ago known as outer radial glial, a secondary population of progenitors now thought to be massively expanded in humans and giving rise to a higher proportion of neurons in the human cortex compared to any other living mammal. By the end of the evening, my mind had been blown so many times, it was a shock that I had a cortex left!

Day four (Wednesday): Standing on the shoulders of giants

We approached the final day begrudgingly, as it had been a truly amazing conference. In the morning Dean Falk taught us how endocasts of fossilised skulls can tell us how brain evolution occurred in our most recent ancestors. This was followed by co-chair Zoltán Molnár (University of Oxford, UK) further delving into the role of the cortical subplate in guiding connections from all over the brain into the cortex. On a side note, some truly awe-inspiring work by Guillermina Lopez-Bendito (Instituto de Neurociencias, Spain) and Rustem Khazipov (Institut de Neurobiologie de la Mediterranee, France) proved without a doubt that pre-birth spontaneous activity in the thalamus and cortex is important in encoding the “programming” of the brain – something that I hope to be able to replicate in in vitro models in the future.

In the conclusions and final discussions, I couldn’t help but offer my thanks to all the academics, and students alike for their contributions to the field and for the amazing research they presented. For a young PhD student like myself it was incredibly formative, and a great opportunity to make many new contacts in a rapidly developing field. As a grand finale we had the time-honoured gala dinner, where Zoltan, Arnold and Pasko gave fantastic speeches, handed out poster prizes (Lorenzo got 4th place!) and offered thanks to Lundbeck Foundation and The Brain Prize for helping FENS host this wonderful conference. It offered me one final chance to interact with researchers I hadn’t yet met, and again gave me lifelong connections to the field I hope to remain in.

To quote the adage, I felt that the strongest theme of this conference was “standing on the shoulders of giants”, meaning that in modern neuroscience, greater truth has been revealed by building on previous important discoveries. Without these passionate academics forging the field, young researchers like myself would not be able to reach the greater heights of science.

Thank you to FENS, IBERC and especially The Brain Prize for supporting me in my ambition to attend this once-in-a-lifetime conference! I have made many new friends, and walk away with far more knowledge and confidence than when I started. I’d also like to thank the MesoBrain project for supporting me financially in making the trip to Copenhagen to attend – it was absolutely worthwhile.

The Brain Prize is sponsored by the Lundbeck Foundation, a Danish foundation who have recently proposed a mandate to support Denmark becoming #1 in the world for neuroscience research.