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Dynamic clamp: Single-cell cyborgs

April 27, 2012

I once talked some engineering students into learning about an electrophysiology technique known as “dynamic clamp”. In trying to explain the technique to them, I realized how poorly I understood it myself! Here I will explain the idea behind dynamic clamp like I did to those engineering students. Rather than discuss how it works, I want to address the reason why it is so useful. So to summarize the technique, dynamic clamp is a way of listening and talking to a neuron with a computer, sort of like a single-cell cyborg. To understand the technical side of it, I suggest some background reading on patch clamp technique. The enthusiastic reader might then attempt this specific technical explanation.

So why is dynamic clamp useful? One answer is that it allows us to reverse-engineer a neuron with greater precision than we can do with other techniques. To reverse-engineer a neuron, we can’t unscrew the parts, so we either activate or deactivate individual parts one-at-a-time in order to figure out what each part does. The other techniques available include pharmacology and direct current injection. Pharmacology (drugs) can be used to turn all the ion channels in all the neurons on or off, but this is very imprecise because you can’t target a single neuron or know exactly how much of the drug actually reached it. Regular current injection can be used to raise or lower the membrane potential (voltage) of a single neuron, but this may affect more than one type of ion channel. Additionally, regular current injection is not dynamic because the computer/amplifier does not adjust the current flowing in and out of the cell based on the changing membrane voltage like a real neuron does. (For the electrophysiologists reading this, note that voltage clamp could be considered the most limited form of dynamic clamp possible. For others, you can read about voltage clamp on Wikipedia and Scholarpedia.)

Dynamic clamp is a dynamic form of current injection. Like regular current injection, it targets a single neuron. However the amount of injected current dynamically changes according to whatever rules you want to program into the computer. One application is to deactivate certain voltage-dependent ion channels on a single neuron. Why would anyone want to deactivate ion channels? Remember we are reverse-engineering the neuron here, so whatever happens without those channels will tell us something about what those channels actually do in the neuron. Suppose these channels open when the membrane potential exceeds a certain threshold but remain closed at lower potentials. In the dynamic clamp approach, we can use a mathematical model of the conductance for these channels to predict what they will do in real-time based on a continuous measurement the membrane potential. The key is that this programmed response is dynamic, meaning it can change in real-time just as the membrane potential of the neuron is changing in real-time.

So not only is it a real-life way to create a cyborg (on a small scale), but it has real scientific value.

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