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What is an Experiment?

What is an experiment?
Experimenting with color (source)

People use the term 'experiment' to meant a lot of things. One may say "she experimented with drugs" or "she performs experimental music". Someone might 'experiment with ones hair' or 'perform a thought experiment'.

All of these uses of the word experiment have distinct connotations, but most of them essentially mean 'to try something and see what happens'. In the examples above, most of the phrases also imply that the experiment is something new. If she experiments with her hair, she's probably trying some new style and seeing if she likes it. If she performs experimental music, she's probably not following the conventional rules for the music she is playing.

Are these kinds of 'experiments' different from the experiments that scientists do? Well yes and no.  The basic definition of an experiment as 'trying something [often new] and seeing what happens' is pretty much what scientists do. So what's different? Why isn't someones 'hair experiment' publishable in a scientific journal?

Mythbusters would have you believe that the only difference between science and screwing around is writing it down:


And that is sort of true.

But what really makes a scientific experiment scientific is controls. In our hair example, you can experiment with your hair by dying it black, and seeing if you like it. But that's not the scientific experiment. To be scientific you would have to decide how to measure how much you like your new hair color. You could do this by filling out a survey each day asking you how many times you thought you were pretty or rating your confidence on a scale of 1-10. You could fill this survey out for a week and then dye your hair and fill the survey out for another week. You could then compare the scores and decide if the new black hair had a 'significant' impact on your self-image. 

Lets say it does impact your self image and you report higher self-confidence that second week. But what if you feel different just because you have a new hair color, not because you have black hair?

Well, you would want to do a control experiment, which controls for the newness of the hair color. You could control for novelty by dying your hair yet a different color, and taking the survey for another week. Or you could take the survey two months after you dyed your hair black to see if you still report higher confidence or if your confidence has dropped back down to normal.


This is not a perfect experiment by any means, it's not even a clever or well-designed one, but it is somewhat scientific. And illustrates what I think is the most important difference between experimenting as in trying something new, and experimenting as in trying to find something out:

The control group


In addition, here is a great example of how important the control group is in science. (See the epilogue)

© TheCellularScale



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Homeostatic platsicity in a thorny situation


Synapses, the connections between neurons can strengthen and weaken depending on the specific activity at that synapse. This is called synaptic plasticity, and we've talked about it a lot on this blog (here, here, here and here).

the strengthening and weakening of synaptic connections corresponds to the spine growing or shrinking (Matsuzaki 2007)

However, there is another kind of plasticity that can occur at synapses. This is called homeostatic plasticity. And instead of the synapse strengthening or weakening depending on the specific activity at that synapse, the synapses strengthen and weaken in homeostatic plasticity depending on the activity of the whole cell.

To drastically simplify, each cell 'wants' to fire about a certain amount, if it suddenly starts to fire a lot less, it will take steps to strengthen its connections or make itself more 'excitable' so it can get back to its preferred amount of firing. Similarly if the cell starts to fire a lot more than normal, it will take steps to make itself less excitable and to weaken its connections until it reaches the right amount of firing. 
Thorny Excrescences from Lee et al., (2013)
A recent paper from the Pak lab explains how in some specific neurons in the hippocampus (CA3 pyramidal cells), the activity of the whole cell is strongly controlled by a some very peculiar synapses. These synapses are close to the cell body, and are on these HUGE weirdly shaped spines (see above) called "Thorny Excrescences". For comparison 'normal' spines look more like this:
Spines from Lee et al. (2013)
The Thorny Excrescences (TEs) are massive spines that contain many separate synapses on them, but connect to the dendrite through 1 neck. 'Normal' spines, on the other hand, usually have 1 synapse at the spine head, and connect to the dendrite through 1 neck.

The size of the TEs, and their proximity to the soma makes them an extremely powerful way to control the signals that the soma receives. Lee et al (2013) shows that when you drastically reduce activity by blocking action potentials (using TTX), you get massive growth of these TEs, but the normal spines further away from the soma stay the same.

They test 3 things to determine whether the TEs have undergone homeostatic plasticity. They look at the morphology (they are bigger), the activity (the electrical signals from them are bigger) and the molecular signatures (the molecules indicative of new synapses are more plentiful). The paper is a really nice complete story showing that these TEs have a lot of control over the general activity of the cell.

It also solves an important problem with homeostatic plasticity. That is, how can the general activity of the cell be modulated without the specific differences between synapses being erased, and consequently the memories or pieces of information they encode? If homeostatic plasticity occurs at spines dedicated to it, then the other spines can still encode specific signals while the activity of the cell as a whole changes.

© TheCellularScale

ResearchBlogging.org

Lee KJ, Queenan BN, Rozeboom AM, Bellmore R, Lim ST, Vicini S, & Pak DT (2013). Mossy fiber-CA3 synapses mediate homeostatic plasticity in mature hippocampal neurons. Neuron, 77 (1), 99-114 PMID: 23312519


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