We both had a typical day at the lab. I woke up at 8:30 and rushed to the journal club (9:00), I then showed some disgruntled students where they can find their enzymes in which of the many freezers, wasted some time on ordering new antibodies and then I tried to book a free slot on the confocal microscope (next Tuesday at 21:30!), I sent out a couple of emails discussing how to go about the new experiments and after lunch I set myself to do more Matlab programming to finally get that analysis program to work, (15:00) reverting to manual data analysis (again) and when all the more productive people headed home I ate a stale slice of pizza that I found in the conference room after some groups’ pizza meeting and after all that I finally got round to doing an experiment.

At the moment I’m using intrinsic signal imaging to measure how responsive the visual cortex is to one eye over the other. Pretty simple, not too exciting but essential for my experiments: relating structural synaptic changes to functional changes after inducing ocular dominance plasticity.

I must say that I cherish these times, using a simple method to collect lots of data fast. As Luther (roughly) said: the work of a women that is merely sweeping the floor is also divine as she does it with concentration and passion.

I must confess that although I’m Dutch my knowledge on calvinism is actually quite limited and I heard the phrase from philosopher Alain de Botton, supossedly quoting Luther. But the point is that it struck a cord. I love science even though sometimes practicing it is frustrating (this is a euphemism). My other half (his name is Laurens) is also a neuroscientist and quite accidentally works in the same institute. His day roughly progressed the same way as mine but didn’t result in the same blissfull data collection. As I said sometimes experiments are frustrating and unfortunately usually the good ones are. After spending 12 hours at work I dragged him home and on the bike I asked him how things had been in the lab.

What followed was a lesson I seem to have to learn over and over again (so much for one trial learning): when someone confides in you with a problem, zip it and don’t start to offer copious amounts of “good advice”.

Luckily, Laurens and I share a passion that we both like to indulge in after being frustrated with experiments which is pretending everything is possible and there are no technical limits to our experiments. It all started on our last camping trip in Amboise (France) where I picked up a little notebook which said le cahier les idées géniales (notebook for ingenious ideas). Usually, people tend to frustrate their thought processes by limiting the feasability of their plans but this childish notebook made us throw all of that overboard. And ever since, we sometimes just let ourselves go and think of crazy cool experiments.

And here’s what it resulted in:

Our lab found that adult ocular dominance plasticity induces a higher turnover of inhibitory synapses that specifically sit on dendritic spines in the most upper layers of the primary visual cortex (V1). We found that those double synapses more often receive thalamic input which led us to believe that probably the adult cortex after monocular deprivation subtly disinhibits eye specific inputs in order to effectively modulate the responsiveness to the open eye. The next question that I had was, where do the eye specific inputs come from? Thalamus, but LGN or perhaps pulvinar (lateral posterior nucleus in rodents)? There is a bit more evidence that it might be the latter and so here’s the crazy cool idea. I inject a tracer that travels from the retina to the thalamus and finally to V1, much like Ed Callaway’s technique. Only now I add channelrhodopsin and make sure I only activate the tracer in the pulvinar with a helper virus. I can then image our in utero electroporated GFP-labeled double synapses and their pulvinar input and then simply increase the strength of the input by shedding some light and of course I would have patched the labeled cell and measure ocular dominance before and after. Yeah right, so what’s your insanely crazy cool idea?

Also read Laurens’ post for more reflecting advice on surviving grad school.