Category Archives: speculation

Lab notebooks, lab websites, the future.

About a year ago I went through a phase of rabid excitement regarding my lab’s website. Then I had to do some experiments, write grants, move across the country. And then today I became rabidly excited again.
Things in the Snyder lab are at a critical moment. My first 2 undergrads have retired, and new undergrads, a grad student, and postdocs have arrived or are arriving soon. Fledgling projects that I initiated are being handed off and I can tell things are going to grow rapidly. Now is the time to institute strange lab protocols so they become the norm. Today’s question is how to keep abreast of it all that is going on. Typically, one uses hardcover lab notebooks and the only person that ever looks at them is the experimenter, and occasionally other lab members when that person has left and there’s work to tidy up. As long as there’s decent communication this model can work just fine. But sometimes communication is hard, sometimes lab notebooks are messy, but most of all, there’s so much more that a lab notebook could be.

My re-rabidness (re-raBIDniss) was spawned as I was passing on my experimental notes to a student. The notes were in a Google doc so I could either copy and paste them, or just invite them to share the document. And if everyone in the lab used it then we’d all be on the same page (whose rats for which expt, who has expertise in certain protocols, general curiosity about lab projects). And then I wondered, is it a concern for one lab member to see another’s experimental notes? It sounds crazy but given the amount of secrecy involved in producing scientific research and the fact that no ever reads another’s lab book I wondered if it might just “feel weird”. Since in my heart open notebook science is the way to go, and since some actually put this into practice, I figure there are no real issues with simply sharing notes thoughout the lab, and any weirdness will be temporary and far outweighed by the positives.

At the moment I envision something like: A WordPress blog as the lab home page, containing links to Google spreadsheets (colony, orders, etc), documents (individuals’ experimental notes), calendars, files etc. But if this is where we go every day to organize our science, why have a separate site to present ourselves to the world? Why not make our lab notebook and lab website the same thing? And that’s where the blog comes in, where we can share data, pretty pix, random lab occurrences, literature reviews, whatever. There would likely be different views depending on whether you’re logged in (a lab member) or viewing from the outside. So this wouldn’t be completely open notebook science or anything, but I think it would help unify many of our responsibilities as scientists, namely to effectively and intelligently plan experiments, record our findings, communicate and educate (of course, great venue for jokes too).

Impaired adult neurogenesis leads to depression – is it realistic?

depressionAbout a year ago we published a paper linking adult neurogenesis to depression. A causal sort of ‘linking’, right? I mean, we found that, when adult neurogenesis was eliminated, mice had elevated glucocorticoids in response to stress and showed depressive-like behaviours1. So doesn’t this mean that impaired adult neurogenesis could lead to depression in humans, in the real world?

Well, it could…and we did end our paper with the following:

Because the production of new granule neurons is itself strongly regulated by stress and glucocorticoids, this system forms a loop through which stress, by inhibiting adult neurogenesis, could lead to enhanced responsiveness to future stress. This type of programming could be adaptive, predisposing animals to behave in ways best suited to the severity of their particular environments. However, maladaptive progression of such a feed-forward loop could potentially lead to increased stress responsiveness and depressive behaviours that persist even in the absence of stressful events.

We had to end it somehow – I was just happy that after 3 years of work we were DONE2! But our final speculation makes it clear that, while this chapter may be done, the story is not. And this fact was rightly pointed out in a recent commentary by Lucassen et al. in Molecular Psychiatry3, where they continue the discussion and bring up some good points. Here is a loose elaboration on some of the outstanding issues they bring up. Continue reading Impaired adult neurogenesis leads to depression – is it realistic?

The National Institute of Replicating Discoveries, Y’all (NIRDY)

Sometimes when you say something on Twitter people respond. People don’t respond that much to what I have to say but, now and then, there’s enough of a reaction to help me realize that an idea was meaningful beyond the moment it popped into my mind and made its way onto the keyboard. So, thanks to those people for starting the conversation.

The idea I had today is that some scientific disciplines could benefit from more replication. And what better way to do it than to have Big Brother audit your science and see if they can replicate in their lab what you did in yours. The idea stemmed from my own feelings about my field. I’ve had serious thoughts lately about trying to replicate a couple findings that have had a lot of influence in the field. They’re important findings. They reveal key functions of new neurons that could be relevant for human health. For this reason the whole field is aware of them, cites them, uses them as justification for additional research. Sooo, then why haven’t they been replicated?   Continue reading The National Institute of Replicating Discoveries, Y’all (NIRDY)

How does the brain pick which neurons to use?

ResearchBlogging.orgWiring. That’s one answer to this question. We know this from topographic maps in the thalamus and neocortex, where the basic units of sensory information are neatly represented in spatially-arranged populations of neurons – the various body parts are represented in specific locations, as are the different frequencies of sound, the different parts of the retina, and different odors and tastes. This basic sensory information has to be represented (i.e. we all need a faithful representation of visual elements, we all need to hear the various frequencies of sound that make up human speech etc.) so why not hard-wire it and make its representation the same for all of us?

It’s often thought that things change as you move into parts of the brain that represent more complex and abstract concepts. For example, in the hippocampus, many neurons receive the same inputs so it’s generally assumed that different neurons are equally capable of representing a given piece of information. While wiring between neurons must play a role in determining which neurons are activated, the diffuseness of the wiring means that related information need not be stored in spatially neighboring neurons as in the sensory regions of neocortex. Indeed, if you look at hippocampal neurons activated by a given experience they don’t appear to have any particular spatial arrangement but are randomly distributed, anatomically. Alternatively, it could be that certain hippocampal neurons are hard-wired to respond to specific stimuli, it’s just that we don’t understand the wiring. Continue reading How does the brain pick which neurons to use?

What IS the dentate gyrus doing to CA3?

Calbindin expression in the dentate gyrus/hippocampus is variable, and particularly weak in young neurons
A fundamental property of the hippocampus is its ability to rapidly encode memories while simultaneously keeping them distinct. Recording from hippocampal neurons one can clearly see that different populations of neurons are active as a rat explores two environments. This is thought to be one mechanism by which information is kept distinct in the brain.

For the last 15-20 years it has been thought that the dentate gyrus (DG), a major subfield of the hippocampus, serves to take small changes in incoming sensory information and orthogonalize them (i.e. make them more different). This idea was built in part on the fact that there are many more DG neurons than upstream cortical neurons. Thus, the DG could use completely different populations of neurons to represent different sets of incoming information and then pass on these representations to CA3, which may bind them into coherent events/memories (the interconnectedness of CA3 neurons, via “recurrent collatorals”, is thought to be a mechanism by which the different components of a memory are bound together).

However, a “problem” arose when Leutgeb et al. found that it is always the same population of dentate granule neurons (~1% of the total population) that are active as an animal explores different environments, even very different ones. This was a bit of a surprise. Still consistent with the proposed role of the DG in orthogonalizing information, however, was the fact that the DG neurons fired (i.e. generated action potentials, which transmit information from neuron to neuron) at different rates/frequencies in the different environments. Thus, changes in sensory information were represented by changes in patterns of activity within the same population of cells, not by recruiting different populations of cells. This is but one study – the question of how the DG encodes and extracts information is far from settled (e.g. what are the other 99% of granule neurons doing? Surely there is a situation in which they are active, no?). But the findings were robust and raise many questions, namely: How does the same population of DG neurons activate different populations of downstream CA3 neurons, during different experiences? Continue reading What IS the dentate gyrus doing to CA3?