June 12, 2008

Liveblogging at "Building Complex Brains"

I'm in beautiful Fiskebäckskil on the Swedish west coast for the 5th Kristineberg symposium "Building Complex Brains" at the Kristineberg marine research station. We arrived yesterday to check into the hotel and enjoy the incredible welcome dinner, but the talks started this morning. The town is right by the sea, the hotel we're staying at is quite nice and the weather has been with us, warm and sunny, so I'm loving it so far. The research station has free WiFi, unlike the hotel, so I'm taking advantage of our extended lunch-break to get a few words down, upload some photos, check some e-mails and so on.

I'll expand on this post during the conference to comment on some of the talks I've heard today. So far, very very interesting stuff, and quite useful for my work. Looking forwards to the forthcoming 3 days of evolutionary neuroscience talks, nice food, sun, sea and socializing.

>Update June 12

The first session of the day was on the subject of evolutionary developmental biology or EvoDevo. I noticed that I'm a lot more familiar with "Evo" than with "Devo", those cell-types and developmental stages flew right over my head, but quite a lot of things stuck with me and very interesting stuff was presented. The second session was on neurotrophic factors, factors that regulate the survival and growth of neurons, a subject I'm not familiar with so it wasn't as rewarding.

I'll just quickly put down some brief impressions and thoughts on the talks that I found particularly interesting.

The first talk was on the evolution of different neuron types in the nervous system. The work presented by Detlev Arendt of the European Molecular Biology Laboratory in Heidelberg highlighted the importance of identifying and comparing homologous cell-types across animals, from the very simplest nervous systems in animals that diverged a long long time ago to the more complex ones in animals that diverged more recently (evolutionarily speaking), to understand how new functions and complexity emerged in the evolution of the nervous system. The focus was on the marine bristle worm Platynereis dumerilii.

The general pattern that appears is that in the early stages of nervous system evolution, neurons had multiple functions, then as these ancient multifunctional neurons generated new "daughter" neurons in evolution, the functions were distributed in a complementary way.

What's interesting for me, is that they have identified nerve cells that release the neuroendocrine peptides vasotocin, gonadotropin-releasing hormone and proopiomelanocortin in Platynereis dumerilii. These are hormones that serve a multitude of functions in our physiology, and there they are in a worm brain. Fantastic. Vasotocin is a member of the oxytocin/vasopressin protein family and since I'm studying the evolution of the oxytocin/vasopressin system in vertebrates, this insight is quite exciting. Obviously this system has a very interesting and very ancient history.

Going back to ancient neurons having multiple functions, the vasotocinergic neurons also express light-sensitive receptors, opsins, like the ones we use for seeing. Does this reflect the ancestral function of the hormones in the oxytocin/vasopressin family? Did this system originate as a signal in the regulation of circadan rhythm or time-of-day-dependent behavior? Are these vasotocinergic cells in Platynereis really the equivalent to the vertebrate oxytocin/vasopressin cells? They seem to express the same profile of genes, but I can't completely discard the thought that it could be a whole different cell type in the worm using the same basic gene "scaffold" as the vertebrate cells.

The next talk was probably the most rewarding because it involved an organism that's very interesting for my work - the lancelet or amphioxus, the most basal close relative of the vertebrates. Jordi Garcia Fernandez of the Universitat de Barcelona presented a perspective of what the study of the genome sequence of the lancelet might give us, in particular with regards to the evolution of the nervous system and body plans.

The position of the lancelet in the evolutionary tree of life makes it very important. By comparing its genome with vertebrate genomes we cover the entire scope of vertebrate evolution and gain the possibility to understand a lot about how the primitive organisms that would evolve into the vertebrates worked. The problem so far has been that the genome sequence has not been assembled; in the database that has been available you can only see a mess of fragmented pieces of sequence which makes you miss a lot of information. So it was very pleasing to hear that the assembled genome sequence as well as the release article will be published next week. I've done quite extensive searches in the database that is currently available, looking for the gene families I'm interested in, but it hasn't provided any information. Hopefully the assembled genome sequence and the first analysis will give me some answers. I'll hold on to some thoughts that came to me during this talk until I've had the chance to read the article on the preliminary analysis.

There was a very interesting sidestep during the talk about the concrete experimental possibilities that are opened up once you know more about the lancelet genome. By targeting the specific developmentally relevant genes and producing genetically engineered animals, it would be possible, at least in theory, to replicate what took millions of years of mutation and natural selection and generate typically vertebrate features in the lancelet. One such feature could be the development of limbs, for instance. It's a captivating idea, but only time will tell if its application lies anywhere in the near future.

A subsequent talk by Shigeru Kuratani of the RIKEN institution in Kobe treated another organism at a very pivotal point in the evolutionary tree - the lamprey. The lamprey, as it compares to other vertebrates, is the living representative of early vertebrate evolution. The lamprey brain lacks some of the features that characterize most vertebrate brains, so the questions that comes naturally is, when did particular features of the vertebrate brain arise and what does the lamprey brain actually reflect? I didn't understand a lot of the developmental biology involved, but it appears that the basic plan and gene expression of the vertebrate brain was already established by the time the first vertebrates came along, which is very interesting.

Even though I don't know much about neurotrophic factors, I found one of the talks in the second session quite interesting. Neurotrophins guide the growth of neurons and regulate neuron survival and death. This has consequences for the development of the nervous system but also for the plasticity of the brain, roughly its ability to adapt itself, memory and cognition. There are two models how brains are "built" - either a finite number of components are produced and put together in a determined fashion, much like a Lego set, or an excess of components are produced followed by a process of adjustment and trimming of the excess. It is in the latter model of brain development that neurotrophins play an important part. Alicia Hidalgo of the University of Birmingham, presented the finding of neurotrophins in the model organism of all model organisms, the fruit fly Drosophila. Invertebrate brains are generaly thought to lack neurotrophic factors, their brain development was regarded as a "Lego set", "hard wired" with little room for adjustment and plasticity. Finding this shared feature between an insect and "higher" organisms opens up for the thought that there is one basic "brain building" model and that it very early on included the foundation for the very advanced and adaptable brain that is present in vertebrates.

>Update June 13

I'm in the middle of a talk about fruit fly smell receptors - multitasking is my thing. The two sessions today have been about genomics, and sensory systems and behavior. The genomics session especially really touched on some pretty interesting questions; I'll update this post after dinner sometime if I have the energy. I updated yesterday's post this morning instead of last night 'cause dinner was so rich and plentiful and included ever re-filling glasses of wine as well as brandy after dessert, so we'll see what happens today.

I've uploaded more pictures on a Flick set; this one is of the research station where the symposium is held.

>Update June 14

Today, the last day, is all about the cortex and the evolution and development of the human brain. There is only time for one session in the morning before lunch and the departure from Fiskebäckskil. I think I'll have time to upload the rest of this post before then, and if not, possibly on the train or when I get back home.

The best talk of the day was held by Ann Butler of George Mason University on the subject of the evolution of the brain circuitry that is thought to underlie conscious experience and higher cognitive functions. In a way, the red thread through the presentation was sort of "the search for cognition" in non-human animals and what it could tell us about the evolution of our own cognition. Now, cognition is a very tricky thing to define - it's a typical problem of having the brain trying to understand itself - but a certain type of electrical activity in the networks that form connections between the brain cortex and thalamus, as well as certain anatomical features of the connections have been correlated to cognition. The cortex is the outermost and evolutionarily "newest" part of the brain, and the thalamus is a more central part that to a large extent functions as a sort of "relay station" of pathways.

The really interesting part is that these special features, or components of them, have been demonstrated in animals as diverse as birds, turtle, frog and fish. So it's possible to "test" the nerve networks thought to underlie cognition in ourselves to the equivalent ones in other animals. Especially birds have demonstrated astonishing cognitive abilities - there are some famous examples: "Betty the crow" can make hooks out of pieces of wire to collect a piece of food; Alex the African grey parrot could recognize colors and shapes as well as quantities up to six and maybe even had a concept of "zero", among other things. When one lines up a chart of the complex networks that are thought to underlie high cognitive functions in humans and birds, the similarities are striking. The challenge is to understand how the similarities and, importantly, the differences are telling, how to stimulate the experimental animal in a way that is relevant to it and make the proper comparisons, and what this as tells us about the evolutionary processes that gave rise to out cortex and our cognition.

The thread was taken up by the following speaker, Jon H. Kaas of Vanderbilt University, who talked about early mammal brains and what they can tell us about our own brains. The successive increase in brain size in our lineage, and the increase in the number of nerve cells that this entails, underlie the complex interactions and regional specializations that make our abilities possible. The comparative studies of small mammal brains, theoretically similar to the original early mammals' brains, could offer us clues to how our complex sensory and motor systems emerged - how we experience the world and how we react to it.

Finally, we heard from Svante Pääbo of the Max Planck Institute for Evolutionary Anthrolopogy in Leipzig on the subject of the genomic perspectives on human origins. I've written about his research on the FOXP2 gene before, but this was a more general talk, only using FOXP2 as an example. A lot of it was on the progress of the sequencing of a neandertal genome, but also of course about how comparative analyses of the human genome and the neandertal genome will shine a light on a very crucial point of our evolution. Will we be able to identify genes that were important in our evolution? Will we be be able to define what it is that makes us specifically human? It's difficult to pinpoint what makes us "so special" when more and more of those traits we jealously guarded as "ours" appear in traces in other animals - perhaps looking at the genome, rather than looking at our behaviors and abilities, will be the key. But to do so we need to know more about that last step in the road to where we are today.

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