Lltp Decay Is An Active Process

If very long-lasting stages of L-LTP involve self reinforcing molecular mechanisms, then L-LTP should in theory be permanent. However, it is clear that L-LTP in vivo, although very long-lasting, does decay over time. How can one rationalize these two observations? One possibility is simply to say that even self-reinforcing mechanisms may not be flawless—any lack of fidelity in replicating the relevant molecules could lead to slow decay over time. This certainly is an important consideration that may apply to both LTP decay and behavioral forgetting. However, a novel and important recent finding from Desiree Villareal in Brian Derrick's lab suggests an alternate explanation. Desiree and Brian showed that NMDA receptor antagonists block the decay of L-LTP in the dentate gyrus in vivo (75; see figure). These findings indicate that the reversal of late stages of L-LTP is an active process, as might be expected if one had to break a self-perpetuating biochemical cycle. These investigators went on to show that the post-training NMDA receptor blockade also enhanced memory retention in an eight-arm radial maze spatial learning task—again, a finding consistent with the idea that synaptic plasticity is normally subserved by mechanisms with the capacity for self-perpetuation, that must be actively reversed for forgetting to occur.

How is the erasure of L-LTP achieved? The answer to this question is unknown, but the authors hypothesize that heterosynaptic


BOX 1 The NMDA receptor antagonist, CPP, blocks the decay of late-phase LTP. Effect of CPP or vehicle on LTP decay when administered 2 days after LTP induction (marked with IIIII). Water vehicle was administered to all animals 1 hour and 24 hours following LTP induction (white triangles). Forty-eight hours after LTP induction, CPP (black circles, n = 4) or the water vehicle (white circles, n = 6, pooled control data as in Figure 2) was administered daily for an additional 5 days (black triangles). Decay was observed in vehicle-treated animals as compared with the magnitude of LTP on day 2 (*p < .05). In CPP-treated animals, the magnitude of potentiated responses over the 3- to 7-day period of CPP administration did not differ significantly from the magnitude of LTP on day 2 (cross, p < .05). CPP was without effect on unpotentiated perforant path responses (black squares, n = 3). Insets show representative traces of perforant path-dentate baseline responses (left) and responses collected 1 hour (middle) and 7 days (right) following LTP induction for vehicle and CPP-treated animals. Scale bar, 5 ms, 0.5 mV. Reproduced from Villarreal et al. (75).

expression, it is intriguing that ERK activation is necessary for L-LTP (9-12). However, these data are suggestive but not direct evidence for a necessity for changes in gene expression in L-LTP.

A final piece of more direct "block" evidence comes from investigating expression of the immediate early gene (IEG) Arc. Arc mRNA is normally present at low levels, and is up-regulated by L-LTP-inducing

Was this article helpful?

0 0
How To Win Your War Against Anxiety Disorders

How To Win Your War Against Anxiety Disorders

Tips And Tricks For Relieving Anxiety... Fast Everyone feels anxious sometimes. Whether work is getting to us or we're simply having hard time managing all that we have to do, we can feel overwhelmed and worried that we might not be able to manage it all. When these feelings hit, we don't have to suffer. By taking some simple steps, you can begin to create a calmer attitude, one that not only helps you feel better, but one that allows you the chance to make better decisions about what you need to do next.

Get My Free Ebook

Post a comment