a report by Ceca Kraisnikovic (Graz University of Technology)

“Patience, patience, patience!” – a rule that you remind yourself not only when you think about the progress made during your PhD, but, in times of the pandemic, also for in-person events crucial to feel that you are part of the research scientific community. Planned for 2020, the Cajal Summer School in Computational Neuroscience could resume only in 2022, and finally welcomed twenty-four participants from different research labs (and countries!), at the Champalimaud Center for the Unknown in Lisbon, Portugal, and during three weeks of wonderful summer weather, July 17 - August 6, 2022.

 

Let the summer (school) adventure begin!

Bom dia, Lisboa! Our advanced training course could start by getting to know each other. Through the quest to match each participant’s project with their name, a friendly atmosphere was established immediately. “Spiking networks on a chip propping up a sinking ship”, the phrase indicating my work on spiking neural networks and their possible use on neuromorphic hardware, put a smile on my face, and we thanked Joe Paton, one of the course directors, for creative descriptions and a pleasant start.

The scientific part of the summer school

The first week started with great lecturers Maté Lengyel, Srdjan Ostojic, Christian Machens, Tim Vogels, and Brent Doiron. Their lectures were followed by exercises that we were challenged to solve. We gave our best, but for some tasks, the hints and help from our dear tutors – Dylan Festa, Francesca Mastrogiuseppe, Carlos Stein, and Janaki Sheth – were very appreciated.

Already in the first week, we learned about the mechanisms of neuronal variability and what effects different noise levels can have on neuronal population firing rates; balance in neural networks and that E and I populations of neurons play a “push-and-pull” game. We implemented a noisy leaky integrate and fire neuron model, and made a large population of uncoupled neurons encode a common time-varying signal given to all neurons as input. To learn about neural data analysis, we used spike data from an experiment with monkeys performing a working memory task in which they had to distinguish whether a stimulus frequency f1 is greater than stimulus frequency f2. We generated Peri-Stimulus Time Histograms and reproduced a few figures from the original paper; we learned that one can use Principal Component Analysis on neural activity exhibiting mixed selectivity to obtain demixed selectivity, subsequently reconstruct full neural activity and get neural representations that are easier to further investigate and interpret. We also studied neural network models as dynamic systems, and how the dynamics of neural networks lead to computations. We simulated a trial of a working memory experiment in which a single neuron could remember a previously presented stimulus through persistent firing.

In the second and third weeks we got to hear also about the experimental work and the approaches to model different phenomena, and, in addition, to work on projects that aimed to deepen our knowledge of a specific topic of our interest. The choice was rather a challenge given that there were many excellent project proposals and possible research directions. My project work considered a minimal recurrent neural network model with restricted connectivity and we investigated its activity in detail via mathematical analysis. We also trained this model via gradient-based methods and reverse-engineered the obtained network. At the end of the project work, we were able to understand the model’s dynamic strategy to solve the task, hence the neural network model was not a “black box” for us anymore.

 

The social part of the summer school

We had a great time not only in the classroom but also outside, during many walks, dinners, gatherings. An amazing boat tour on the river Tejo, with a dinner and party, gave us hard time getting up on time the next day, but frequent coffee breaks made it possible to still follow the talks and productively work on our projects. We also had an opportunity to challenge ourselves in surfing, testing how fast our motor cortex can learn. It was certainly great fun!

This summary is definitely too short to describe all the content and our personal experiences during three wonderful weeks at the Champalimaud research center. I was really fascinated by everything we experienced there, both in terms of knowledge and the ways we socialized. A very remarkable summer school, and I highly recommend this (and all other) Cajal summer schools to all neuroscience PhD students!

Additional information about the summer school can be found here: https://cajal-training.org/on-site/ccn2022/

 

Lastly, many thanks to…

Course directors (Brent, Joe, Julijana, Maria) and tutors (Francesca, Dylan, Carlos, Janaki) for their advising and time spent with us; course organizers Teresa and Joana, for being there for any request and wish from our side; course presenters, for presenting their admirable research; course participants, for a great time, fun, deep conversations, invitations for going out; my hotel-roommate Johanna Frost Nylen, for the conversations about science, research, life, society, culture, ocean, Sweden;

mentor Robert Legenstein, for his supervision and patience; professor Wolfgang Maass, for earlier supervision and supporting my application; secretary Daniela Windisch-Scharler, for having an answer/solution for any bureaucracy issue; my research lab, Institute for Theoretical Computer Science (IGI), TU Graz, for making this summer school attendance possible; and Austrian Neuroscience Association (ANA), for partial financial support and promotion of science and research.

Ceca Kraisnikovic
Graz University of Technology
Graz, Austria

 

Clock entrainment by sun- and moonlight in Platynereis dumerilii

Animals possess endogenous clocks to anticipate cyclic environmental changes. Ambient light is one of the most important cues to synchronize internal timing systems with these environmental cycles. While moonlight is well known to entrain monthly calendars  (circalunar clocks) in some marine species, sunlight is the main entrainment cue in most species for the daily (circadian) clock. However, there is growing evidence that moonlight also affects daily timing in various species, ranging from invertebrates to humans. How moonlight affects the circadian clock, and how the circadian clock actually discriminates between moonlight and sunlight, remains largely elusive.

In my thesis, I used the marine bristle worm Platynereis dumerilii as a powerful experimental model system to assess how moonlight affects circadian timing (manuscript 1). By establishing a novel behavioral paradigm, I showed that circadian timing of the worms’ reproductive behavior (swarming) is governed by a moonlight-sensitive plastic circadian clock  that times swarming onset to the respective portion of the night where no moonlight is present.

I then used this experimental paradigm to work out key genetic factors involved in this process. By testing Platynereis mutant lines that are deficient in candidate photoreceptors, we identified two photoreceptors, L-Cry and r-Opsin1, that are required to correctly adjust the circadian clock to nocturnal moonlight. While r-opsin1 is genetically required to adjust circadian timing of swarming onset to moon phase, L-Cry seems to be required to correctly discriminate moonlight from sunlight. We extended this finding to the fruit fly model Drosophila, were we showed that the respective L-Cry ortholog is also required to correctly interpret ambient moonlight, preventing a disturbance of the circadian clock by moonlight. Together with a companion study (manuscript 2) that investigated the function of L-Cry in the context of the worms' monthly circalunar clock, these findings provide first molecular insights into the decoding of moonlight versus sunlight for circadian and circalunar timing.

We all have to watch what happens in the Ukraine. Please note what FENS has posted on its Website. As scientists we may be "apolitical", but we are not blind or deaf. So let us stand together with our colleagues and see how we can help.

ANA member Cornelia Ablinger (Karl Landsteiner University Krems) was selected to participate in the Cajal Training Course “Optogenetics chemogenetics and biosensors for cellular and ciurcuit neuroscience.” Congratulations! ANA provides grants to support participation in Cajal Training Courses. Cornelia was one of the grant awardees. Read Cornelia´s report about her experiences at the course in Bordeaux.

Personal motivation and background

A Year ago I was very excited to be in the position for applying for a Cajal neuroscience training programme. Epecially during the pandemic it seemed almost too good to be true, that I may get the chance to travel abroad to attend an international training experience. One year after I sent the application and very patiently waited for my acceptance I am still excited and grateful that I not only was entitled to participate in the course consisting of only 20 students, but also that the course finally could take place in person in Bordeaux! Especially as Austria went into lockdown the day after my flight to Bordeaux, I appreciated it even more that the organisers and instructors of the course, despite the uncertainties of the pandemic, put so much effort into making this course possible. The “Optogenetics chemogenetics and biosensors for cellular and ciurcuit neuroscience” course immediately caught my attention on the Cajal training website as it was matching closely what I was currently working on and planning to work on in the future. The projects sounded amazing with all the fancy tools and methods and indeed the course directors did not promise too much - we really had an incredibly informative course with state of the art tools and devices for hands on training and very rewarding scientific discussions. It was a pure pleasure to be part of this great experience and meet amazing people from whom I could not only learn a lot but also share my joy of doing and discussing science and new ideas.

Excellent course infrastructure in Bordeaux

The course directors Ofer Yizahr, Michael Lin, Simon Wiegert and Anna Beyler are not only very nice, friendly people, but also true experts in their fields! They employ precise manipulation and read-out of brain circuit functions using genetically encoded tools to measure and control neuronal activity in not only single synapses but also large scale circuits to investigate brain function. As the field of genetically encoded sensors has exploded in the recent years, the speakers in the course had a challenging task to cover all the aspects and they did an incredible job in teaching us about which tools are available and what are the advantages and disadvantages of using them. They also explained what technical challenges have to be considered and were happy to discuss these topics with us in depth, to help us with our struggles and particularly to overcome these in our own research. In the 3 weeks of the course, we indeed learned a lot about optogenetics, voltage and calcium indicators, enzymes and neurotransmitter indicators, and G-protein coupled receptors. Most importantly, w had the chance to acquire hands on training and experience in  these techniques in small groups (2-3 students) in two projects.  Moreover, we had workshops to introduce and help us with deep lab cut, matlab and python- for me personally this was the most challenging part, as I had zero coding experience.

I also would like to mention that without the guidance of our excellent instructors, none of the projects would have been possible and I am very grateful for their help and advice throughout the course. Of course, also the facility of the Bordeaux school of neuroscience and the Bordeaux imaging centre contributed enormously to the success of the projects as they provided us with the facility and the newest equipment and microscopes.

Scientific projects

During my first project, I was able to perform stereotaxic surgeries with fiber implantation, perfuse the animal and validate the surgery injection, set up and perform dual fiber photometry recordings using GCaMP6s and jRGECO1a as calcium sensors and monitor the transients in behavioural test such as elevated plus maze and open field test. Moreover, we were introduced to specific data analysis tools and benefited from the amazing programming skills of our instructor Praneeth Namburi.

Within the second project, I could learn how to implant a cranial window with a head bar, learn to train and head fix a mouse, set up and program a whisker stimulation together with optogenetic stimulation for head fixed mice. I was also able to perform in vivo calcium imaging using a 2-photon microscope with an axonal GCaMP7b and perform optogenetic inhibition of thalamocortical projections using eOPN3. Our instructor Mathias Mahn was very patient and helped us to troubleshoot a lot, not only during programming and setting up the system, but he also raised good points of discussion during the analysis.

Summary and outlook

Overall the Cajal course offered me a huge opportunity to not only learn new techniques, but also to get to know new people, to discuss with instructors, speakers and organizers in a more familial manner than at international conferences. The main reason for the many extensive discussions was the outstanding motivation of all students, speakers, instructors and course directors. All instructors and speakers were super friendly and nice people, which made it instantly easy to get into a conversation and to get along and collaborate very well. For me the course was a unique chance to broaden my educational background and get international feedback on my current and future projects, which was very rewarding and a highlight in my scientific career so far.

Finally, I would like to acknowledge the support at home that helped me to attend this course. I especially thank my supervisor Gerald Obermair, who very much encouraged me to apply for the course – he always rated my chances of being accepted for the course higher than I did and in the end, he was totally right! I am also very grateful for the generous support from the Austrian Neuroscience Association (ANA), which made it possible for me to attend the course. You can find the list of upcoming Cajal courses here: http://cajal-training.org/courses/

For more details to the course or detailed information on the instructors and speakers of the course please visit:  http://cajal-training.org/on-site/ocbccn2021/

The best advice I got was to apply for the course so I can only advice any student or post-doc to do the same!

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Sandra Apler is mother of a small boy who suffers from a mutation of the Syngap 1 gene. She has set up the non-profit organization Leon & Friends which aims at supporting Syngap1 children and at driving research for treatment.

Leon and Friends were the main organizer of the first (virtual) European Syngap1 Symposium (March 15-16, 2021). As ANA we are happy that we could assist in setting this up.

On March 15 2021, Austrian radio Ö1 aired an interview of Sandra Apler and Simon Hippenmeyer (Dimensionen, die Welt der Wissenschaft) by the Ö1 science journalist Marlene Nowotny. ANA received permission to stream this interview.

Investigating the neuronal basis of magnetoreception in the pigeon
Simon Nimpf (IMP Vienna)

The remarkable ability of animals to navigate over long distances is mediated by the sensory perception of the Earth’s magnetic field. Behavioral experiments on a large number of taxonomically diverse species support the existence and utilization of magnetoreceptive systems, however the underlying sensorineural structure mediating this unusual sense remains elusive. In this thesis I set out to investigate where and how a magnetic stimulus might be transduced into a neuronal impulse and how this information is integrated in the central nervous system of pigeons.

Employing neuronal activity mapping I report that exposing pigeons to rotating magnetic fields leads to increased activity in the brainstem vestibular nuclei and the hippocampus of pigeons. Physical calculations and modeling further support the hypothesis that magnetic fields might be detected by voltage sensitive ion channels in the semicircular canals of the vestibular system through a process called electromagnetic induction (Nimpf, Nordmann et al., Current Biology, 2019). Using a newly established in vivo 2-photon calcium-imaging set-up, I provide additional preliminary evidence for magnetosensitive neuronal populations in the pigeon hippocampus. Finally, I investigated the molecular machinery associated with the formation, development and function of an iron-rich organelle in pigeon sensory hair cells and its potential involvement in magnetoreception (Nimpf et al., eLife, 2017). Taken together, these data support the hypothesis that magnetic field information might be detected in the pigeon inner ear and relayed to higher order brain structures for central integration.

Jury for the 2020 Best Thesis Award: Thomas Klausberger (Loewi Award 2005); Alex Koschak (Loewi Award 2011); Daniela Pollak (Loewi Award 2009).