Well, we've discussed some interesting issues. For some reason, it seems that the advancement of neuroscience is linked to technology. In 10 years time we may have more regulations for working with animals, although they remain our main source of knowledge. We are still skeptical enough to think that in 10 years we will be able to read minds or download the content of the brain to a computer, we will be more optimistic in the future? In fact, those who discussed what neuroscience will be like in 50 years think that we will have several ethical problems to solve, to which will be added some related to the security of the data that could be obtained from our brain. Someone even considered that we will develop for that time neurohadware. What do you think? Our dreams become even more complex when we think of 100 years in the future. If you think there will be links between brains or between brains and machines, you may not be very wrong.
At this moment we are gathering 80 doctoral students from all disciplines to share an amazing experience. We thank the sponsors and participants who made this meeting possible. With an interesting program that has researchers from all over the world, we will explore the road ahead of neuroscience.
The professor emphasized that the brain is a complex structure and that will not be easy to unravel. Memories and signals from the brain are encoded as electrical signals in the neurons, but we are just beginning to unravel the mysteries of the brain.
Professor Knöpfel agrees with our students, what we can know about the brain is linked to technology. Technology is the gateway to knowing the brain and the mind. Electrophysiology has allowed us to know the properties of individual cells and groups of cells. Now, !we can see the electrical signals as if they were light! The fantastic approach that allows us to do this is optogenetics. "For me, optogenetics started 10 years ago," says Professor Knöpfel. With this method, light can be used to modify simple or complex cell dynamics. However, in the opinion of the researcher, although light is much more convenient for us, we cannot abandon classical electrophysiological techniques, in fact, optogenetics is a complement rather than a replacement for electrophysiology. "The good thing about optogenetics is that you can know what you are doing, what you are stimulating".
How can you study the state of a cell, if optogenetics modifies the metabolism of the cell itself? asked one of our students. “I don't have a precise answer for that, because it's actually a problema”, the researcher replied, and added, "There are several possibilities, we can establish indicators that remain constant, even if we modify the properties of the cell membrane. The researcher commented "the principle works, otherwise I wouldn't be here". Optogenetics is a broad tool and can address a wide range of individual and collective cellular behaviours. The activity of different parts of the brain at different scales of time and space can be explored. In the presentation it became evident that calcium ion measurements are prevalent in this field, because the fluorescent proteins used in the technique are mostly linked to calcium channels.
After giving us an overview of his last 15 years of research, the researcher encouraged the students to continue their efforts "Don't give up when you see that something is too difficult or impossible".
Alzheimer's is a well-known disease that affects a large population around the world. Loss of neural connections, circuit failure and cell death are some of the consequences of the disease. The laboratory of researcher Nancy Ip focuses on synaptic dysfunction and neuroinflammation in this context. Although much has been studied about this disease, we still do not know the pathophysiological mechanisms underlying the disease. "Understanding them will allow us to think about some interventions," says the researcher.
Professor Ip indicates that loss of synapses precedes loss of neurons. We found in a study of 80 patients that cells reduce their metabolism and their number of dendritic spines, she says. She points out that in about 7 years of work they have discovered that the activation of EphA4 reduces the number of dendritic spines, linked to interactions with cdk5 proteins and AMPA receptors, among others. Similarly, the researcher suggests that the presence of this protein in animal models reduces synaptic plasticity. "Identifying a specific EphA4 inhibitor would allow us to develop a therapeutic mechanism to combat the disease”. Surprisingly, some of these inhibitory components, such as Rhy, have been obtained from an ancient technique: Chinese medicine. After all, in various areas of knowledge, we return to our roots.
In addition, the production and deposition of Aβ is a mechanism that can severely damage cellular function. "It is also necessary to work on mechanisms to clean the depositions of this protein” she conclude. In this context, the researcher draws attention to microglia. She states her research suggests that the onset of symptoms of Alzheimer's disease is linked to a malfunction of the microglia and some of the cytokines they secrete. In particular, it appears that cytokine IL-33 has a strong association with the disease, at least in the Chinese population, where one of the studies was conducted. The researcher and her research group found that administration of IL-33 in mice improves symptoms of the disease, assessed through behavioral testing. In some way, this is a very good input for those researcher who think the brain in much more tan neurons.
In the session on pathologies and new therapies, Dominique Fernandes from the University of Combria in Portugal showed us the importance of the CASPR2 protein in brain pathology. CASPR2 is an adhesion molecule that forms complexes that contribute to the grouping of the potassium channels in the axon of the cell. However, this well-known ro ro does not explain the symptoms in people with mutations in this gene. This is the problem that this researcher addresses in her doctoral research. Their research indicates that CASPR2 plays a role in the traffic of glutamate from AMPA receptors. Research with knockout mice suggests that the absence of CASPR2 reduces AMPA receptors in cortical neurons, affecting gluatamatergic transmission in the visual region of animals. The loss of glutamatergic transmission may be a mechanism behind the homeostatic alterations present in various psychiatric pathologies.
Subsequently, Konstanze Simbriger reported on her research into Autism Spectrum Syndrome, focusing on Fragile X Syndrome FXS. The researcher focuses on MMP-9, a protein found in elevated levels in people with Fragile X Syndrome. Research with transgenic animals that over-express MMP-9 has determined that mutant animals develop phenotypes similar to those of people suffering from X Syndrome FXS. Behavioral evaluations of mice have allowed to determine the existence of repetitive behaviors, avoiding new social interactions, which are related to changes in dendritic spines. "The autism spectrum is quite broad and it is difficult to determine specific factors, however, this is a promising principle for understanding some of this disease," says the researcher.
Charline Peylo
Perception seems much more an active than a passive process. Top-down expectations are assumed to be implemented by mental templates. An example could be that when you enter a ktichen, you are more expected to spot a fridge, than a sofa. This leaves the question of how sensory input and mental templates are matched. A prevailing assumption is that brain activity at different frequencies couple in this matching process, namely theta-gamma phase coupling. Charline investigated theta-gamma phase coupling in a novel task, where mental templates have to be formed during the task. She found that the amount of theta-gamma phase coupling is related to the quality of the mental template formed.
Place and grid cells encode spatial information in the brain. Whereas place cells are assumed to remap in different enviroments, which allows to differentiate between different contexts, grid cells seem to be stable and universal. However, the stability of grid cells has been demonstrated so far mostly in squared flat areas and for more distorted and curved environments, there are indications of remapping in grid cells. Davide explored in his talk, whether these remappings could serve to encode multiple environments. He found that remapping would allow grid cell networks to indeed store multiple environments and could show that the hexagonal grid level observed in biological networks has the highest capacity due to high robustness against noise.
Keywords in open science
What is open science?
Openly creating, sharing and assessing research, wherever viable.
Comments from the audience: Is this a solution to the reproducibility crisis? Could this speed up research itself? Important point could be publishing negative results... Who is the audience, only being open among scientists or also integrating the public into research findings? You can already open up, not by disseminating directly, but choosing a form of publication that allows free replication.
What does open science look in practice?
Disrupture of the current system or open science in the existing system?
The ocean picture: research consists of many aspects, of which some are very visible like social media, blogpost, some are very hidden like funding proposals, data and some in between like posters, presentations, ...
Open practices from parts of the research workflow: Discovery, Analysis and Publication
"What happens on that Friday night when after many years of work you finally submit that paper? It is important to demystify publishers. We ourselves are scientists, the editors are here to help scientists to publish. We are here to approve the science you do with high standards”. With these words, Paul Bolam, co-editor-in-chief of the European Journal of Neuroscience, began his workshok on the publication process. And he adds, "The peer review system ensures the validation of the scientific method, quality control and scientific reporting. "It is the task of all scientists to contribute to the peer review system."
How a paper is handled after submission, what editors do, what reviewers do, ethics in publishing, were some of the topics covered by the workshop. In the European Journal of Neurosciences all manuscripts undergo quality control before being reviewed by the publisher. The first step is to explore whether the article meets the minimum format and requirements, the availability of unpublished data and the quality of English. With these criteria met, the article is passed on to external reviewers. The reviewers are on the task of "making sure that their science is of high quality and reproducible," says Professor Bolam. Perhaps something unknown is that the Journal was responsible for reviewing the reviewers' comments: is the review fair? The review presents a bias? The review is out of context?
What editors and reviewers want is your research is novel and important, the conclusions supported by the data, and adequate statistical procedures, among others. Then, the doctoral students had the opportunity to appreciate some examples of reviews, good and bad, that were made in the discipline.
After a day full of science, we have the opportunity to explore another perspective to get closer to the brain. Art, despite being considered a different way of knowing the world, can tell us a lot about how our mind works. Carolien Hermans, a choreographic teacher based in Amsterdam, has worked for several years in dance as a tool for dealing with mental disabilities. "Dance and music are two tools that affect the brain in different ways.... rhythm is very important," she says. The teacher works with a model of active cognition called participatory sense-making "The experience of the body is a very important element for communication and the senses". For several years, the choreographer has worked in institutions with different communities of people with different abilities.
"We are not aware of this, but when we dance we anticipate movements and when we work with children we can observe and analyse these behaviors", says the professor. Through educational videos, the doctoral students had the opportunity to detail the situations in which this work is carried out with children. Caroline is very interested in the intentionality of the movement and the way people use their bodies to socialize in different spaces.
Our second speaker was Kalina Bertin, a film producer who portrays the effect of bipolar disorder on her own family. The experience is shocking, the film production shows us the different phases that his siblings go through during the cycle of depression and mania characteristic of the disease. "I wanted to explore more deeply that world that was so real to my brothers, and in virtual reality I found an interesting tool to explore". And he adds, "Virtual reality becomes a tool for understanding how other people see the world". How do you represent the world of bipolar disorders? How is reality captured? To do this, the researcher referred to psychiatrists and neurologists to collect data. "I needed as much data as possible to replicate the reality of psychosis in virtual reality." However, I soon realized that biometric data was not the answer I was looking for. So I decided to refer to the disease itself, to the symptoms themselves. "I decided then to create a world of recurring symptoms to see if my brothers identified with him" relates Kalina. In bipolar disorder there is a recurrent cycle in which the patient must go through the same cycle from depression to psychosis over and over again. The artist then developed six different virtual environments to represent the world and symptoms of bipolar disorder. This is a very good example of can you can bridge arts and science to treat mental disorders.