More Evidence of LTP in vivo

I wrote earlier this week about evidence from electrode arrays that LTP occurs in vivo in behaving rats ("Rats, you behave!"). The paper showed that if you use an avoidance learning paradigm you can detect LTP in the hippocampus after one trial. The paper does not, however, necessarily prove that this LTP is actually necessary for learning (although there is a huge body of evidence in vitro that suggests that this is the case).

Another paper in Science rectifies that deficiency. Pastalkova et al. also show in Science that if we infuse an inhibitor to a particular enzyme into the rat hippocampus we can destroy a previously acquired memory trace.

The protein is called PKMzeta. PKMzeta has been shown to be necessary for the maintenance of LTP.

What the experimenters do is use another avoidance learning paradigm, but this time the setup tests spatial memory. The rat is placed in a slowly rotating round box with a red area delineated. Inside the red area, the rat recieves a shock. What you can show is that if the rat is placed in the box, it will rapidly learn to stay out of the red area, and that performance staying out of the red area is correlated with LTP.

But here is the interesting part. You then infuse an inhibitor to PKMzeta into the hippocampus after the long-term memory to stay out of the red area has formed (about 24 hours). What you find is that A) the LTP goes away and more importantly B) the rat no longer remembers to stay out of the red area. The performance returns to baseline.

Click to enlarge. You can see in A a picture of the apparatus. B shows where the animal whether treated with the inhibitor (ZIP) or just saline would have recieved foot shocks in a sample experiment -- the animal recieved shocks if it wanders in the pie shaped area.

C shows the improvement in performance over the time after the initial training period. You can see in the bottom right corner how if the inhibitor is infused at 24 hours the performance returns to training levels. Finally, you can see that if we look at time spent inside the red zone comparing saline (control) and inhibitor, the inhibitor for long term memory (LTM) as opposed to short term (STM) returns performance back to pretraining levels.

What can we take away from this paper?

• 1) This is another resounding piece of evidence that LTP is necessary in vivo for learning and memory.
• 2) PKCzeta, a kinase, is necessary for the maintenance of memory at this time scale. This is particularly interesting because it is somewhat counterinituitive. You wouldn't think that you would have to have a constitutively active enzyme to maintain a memory. This work shows that you do. The field of LTP maintenance is an interesting and large one (no time to talk about it now), but what we are learning from it is that maintenance of memory is an active rather than a passive process.

Hat-tip: Faculty of 1000.