Thursday, March 26, 2009

Electrophysiology isn't a technique you add to your CV; it's a state of being!

Neuropharma's comment on my last post contained something that stuck in the craw of this old electrophysiologist. Some grad student she knew thought he could waltz over and learn some electrophysiology right quick, and include it in his thesis.

Then reality struck this student, rapidly disabusing them of this conceit:
"He was shocked to discover that it would take him such a long time to learn the technique (he's starting from level 0) and said that it seemed so easy when reading it from some published paper!"

Every newb thinks that a technique they haven't mastered is easy, until they actually try it. And in fact, the bare bones mechanics of patching are pretty straightforward. I've taught a lot of novices how to patch, and by and large they can get to the point of gigaohm seals in a week or two (ok, we're talking transfected HEK cells here). Hell, I'm thinking any primate above lemurs could learn to get seals. (Not a bad idea actually; screw those automated patch systems, gimme an army of squirrel monkeys and an old warehouse, and I'll screen your chemical library right quick! It'd be like the nut shelling squirrels in Willy Wonka. And they'd literally be DrugMonkeys! LOLZ.)

But there's a huge distinction between the currents you're recording at that point, and 'good' currents. These first currents are crap, e.g. the leak is terrible, the series resistance is awful, the throughput stinks, the solution applications kill cells or generate huge noise, you've got visible 60 Hz pickup. At best they're barely interpretable. But Electophysiologicus will dole out a decent cell here, a nice recording there. That'll be just enough to keep you coming back for more, and to keep the image of good recordings in your mind's eye.

The transition between the crappy recordings of the apprentice and the regular good recordings of the master takes a long, long time, on the order of a year I'd say.
These are the dark times, where the progress is non-existent, perhaps to a greater extent than an analogous part of the curve for other technical subspecialties. Most electrophysiologists I've talked with had this time in their training, typically falling into the 2nd year of graduate school.

And yet, there's very little useful advice the masters can give their apprentices during this time, other than "keep at it". Sure, there are suggestions to try this, or don't do that. In the end though, everyone just has to put in their time, slowly perfecting each requisite skill, and evolving their own personal technique. It sucks, for sure, but it does end.

It's just not gonna end before your rotation or your last few months before you finish your thesis.


Ambivalent Academic said...

Ah yes, Grasshopper. It sounds a lot like microinjection.

Comrade PhysioProf said...


Dr. Jekyll and Mrs. Hyde said...

Six years later, I only feel like less of a newb when I'm teaching an actual newb, like a rotation student.

Anonymous said...

I found this page by googling "I hate electrophysiology." However, I don't see the word "hate" here anywhere. There's nothing like being a 6th year grad student and spending an entire weekend in lab only to get no decent recordings. I will kill myself before ever reaching Master stage.

Anonymous said...

Anonymous, I feel your pain...I am doing whole cell recordings. Not much better. I have gone more than two weeks without a decent recording and I feel highly incompetent. The cells suck. I hate electrophysiology! There!

Nat Blair said...

It's ok anonymous (both of you), we've all gone through it. Hell, right now I myself and suffering through a crappy period of shitty cells and few usable recordings. It's just I have the benefit of knowing that it's the cells, not me.

I can definitely remember hating electrophysiology. I'm thinking somewhere circa 1999 (memory is fuzzy, lack of sleep from two whelps has depotentiated a LOT of memory holding synapses). It was awful. At least my thesis advisor was the ever optimistic type, so that helped.

And you can do it too. Good recordings will come!

Still, doesn't hurt to prepare a few burnt offerings to Electrophysiologicus, just in case!

Nat Blair said...

Heh, and arguably the best part of the Anonys' comments is that now when you google "i hate electrophysiology", this page is the FIRST page in the list. HAHAHAHAHAHAHA

So I now open this up for all manner of venting about how electrophysiology sucks, my seals suck, my pipettes suck, etc.

Go crazy!

Anonymous said...

It's comforting to see I am not the only one struggling...
Days without a cell and wasted two litters of transgenic mice that are hard to come by.
Electrophysiology I want to break you!!!

Nat Blair said...

Hang in there Anony! You can do it. You just gotta give it time and effort, but it will happen.

Mikroenjeksiyon said...

Thanks a lot!!!!
So Gooood Page..….
NIce post

Estep said...

This post made me feel so much better about being a 2nd year grad student trying to fumble my way into becoming a decent electrophysiologist.

Nat Blair said...

Without a doubt, the 2nd year as a grad student mastering electrophysiology is the worst.

The new glow of joining the lab is over, you've gotten your first seal, have enough recordings to know your early recordings stink, but haven't a concrete clue how to progress to make things better.

And yet all I can say is, it WILL get better. It does, at least for those with the grit to stick it out. So hang in there!

Anonymous said...

I found this site by searching for "mice suck for ephys", and they do. They are hard to record from, and they are destroying me. Anyone have suggestions on how to work with them, they are not like rats?

Anonymous said...

I feel better knowing I'm not alone in my pain. I'm at the end of my second year, and just spent a month with zero decent recordings. It's very frustrating when hard work doesn't seem to have a pay off. It's good to know it's not just me.