We take for granted our special ability to describe abstractions - such as "tomorrow" yet such abstractions are only made possible by language.
-Donald B. Calne , within reason
The limits of my language means the limits of my world.
-Ludwig Wittgenstein
New research from the Netherlands Institute for Neuroscience shows that chandelier cells, a specific type of brain cell, become active during unexpected situations. “Researchers have been wondering about the functionality of these cells for a long time”.
You’re cycling to work through the city and suddenly you see a new building somewhere. On the first day that is very surprising. On day 2 this diminishes somewhat, and after a week you no longer notice it at all. The same thing happens the other way around: when a building that was always there suddenly disappeared, you are also surprised. But how does your brain signal unexpected changes and which cells are involved?
To learn more about this phenomenon, Koen Seignette from Christiaan Levelt’s lab joined forces with his colleagues from the Kole lab and Roelfsema lab. Together, they investigated a special type of brain cell found in small numbers in the cortex: the chandelier cell. In contrast to other inhibitory brain cells, they only inhibit one spot of other cells, but there is remarkably little known about why and when.
New mouse model
Koen Seignette: ‘We already knew quite a lot about the function of most types of inhibitory brain cells, but chandelier cells were a mystery. This is because they are not clearly marked genetically, and so could not be properly examined. We have now obtained a mouse model in which the chandelier cells are fluorescently labeled. This allows us to image them live and determine when they are active. That offers new opportunities.’
‘As a first step, we looked at what chandelier cells in the visual cortex respond to. What happens to these cells when the mouse starts running or when we present visual stimuli? In one of the experiments we had the mice walk in a virtual tunnel. When the mouse ran, the tunnel moved, and when it stopped, so did the tunnel. Using this setup, we could create an unexpected situation by stopping the tunnel while the mouse was still running. It was during these events that the chandelier cells started firing like crazy.’
Plasticity
Christiaan Levelt: ‘We see that the type of stimulus does not actually matter that much, what matters is that it is unexpected and surprising. We also noticed that habituation and change occurs, comparable to the aforementioned example of the new building. At first the cells react strongly, but after repeated exposure the activity becomes weaker. This shows that the cells are able to adapt, which is a concept known as plasticity. This plasticity also occurs at a structural anatomical level: we can literally see changes in the synapses chandelier cells form on other brain cells.’
‘What makes this study important is that this is the first really comprehensive study of chandelier cells in the visual cortex. We have not only determined what they respond to, but also which brain cells they form connections with, and what their influence is on other brain cells. This has never been looked at in such detail before. Understanding the role of these inhibitory neurons in the cortex is crucial for many processes, including learning from unexpected circumstances. We all know that you remember things better when it really surprises you. If the prediction is incorrect, that’s where you can find the information. You need plasticity to update your insights, and these cells could play a role in that.’
Why are chandelier cells so special?
Chandelier cells, named for their resemblance to a chandelier, are inhibitory brain cells that focus on the starting point (axon initial segment) of electrical signals in the pyramidal cells, the most common cells in the cortex. It was thought that chandelier cells could exert strong control over pyramidal cells by blocking the action potential. Surprisingly, the current research shows that this effect is actually very weak, which contradicts previously drawn conclusions.
Morphological differences between thorns, spines, and prickles
The limits of my language means the limits of my world.
-Ludwig Wittgenstein
Come up with an idea, define an interesting problem
Do thorough literature research. Maybe similar stuff was already done. Define the knowledge gap well.
Plan in detail, how we can solve the problem, design experiments
Reach out to potential collaborators, agree with them on a plan
Buy necessary equipment, chemicals
Do pilot experiment, optimize the conditions to get reliable data
Perform experiments, calculations, make everything multiple times so it's reliable
Analyze the data
Urge collaborators to deliver their parts
Coordinate your progress with the collaborators
Manage the collaborations, organize meetings
Be diplomatic, you don't want to make enemies in academia
Agree with direct colleagues, who worked on it, what will be the message of the article. Will it be a long story and we need to add some more data? Or will it be short and right to the point and we write a short "letter"?
Do literature research again. Maybe new stuff appeared, and for sure your data must be confronted and discussed with already known facts.
Write the first draft of the article
Send it around for feedback, first only to direct colleagues from your lab
Incorporate the feedback, maybe do more experiments and more analysis
Rewrite the manuscript
Send it around the second, third, fourth, fifth... time
Incorporate the feedback
Send the manuscript to all collaborators.
Wait for the feedback, urge everyone to give it, maybe you don't have all data from all the collaborators yet
Incorporate feedback
Prepare the manuscript for journal submission
Get approval from all co-authors
Submit the manuscript
Wait for editor response, hopefully they send it to reviewers. If not, you need to rewrite a bit the article to adhere to the new journal's format and send somewhere else.
Get reviewers' reports, deal with them, reply truthfully, make effort to explain everything even if you know that the reviewer's suggestion is just impossible or irrelevant. Be diplomatic.
Maybe you need to do an additional experiment, analysis, or rewrite a major part fo the manuscript. This can take months.
Submit revised manuscript with all the changes
Wait for editor's nad reviewers' comments in the second round. You can get many rounds of review and still get rejected.
Finally get a "Congratulations, your manuscript has been accepted for publication"
Pop a shampagne! You deserve it!
BSc. and MSc. students: Perform experiments and analyze data
PhD students: Do all the experimental and analysis parts, write the manuscript, discuss with their supervisor and direct colleagues, incorporate feedback. But does not have to come up with their own idea and manage collaborations and diplomacy.
Postdocs: Do literally everything on the list
Group leader/Professor: Do the thinking and managing parts, help with writing and feedback, provide discussions and insight. Do not perform actual experiments and analysis.
As such, we just have to do all these tasks. It's stressful. It's challenging. It's definitely not boring. I am taking every opportunity to get a student, who can help with the experimental repetitions so I have time for all the other stuff.
Thinking thoughts
Lucian Black, Luciferian Order
Ask yourself at every moment "is this necessary?"
Wake up babe new aperiodic tiling dropped
Aperiodic tiling with only one tile!