8/31/2006

Molecular Basis of Memory Consolidation

Although memory erasure has long been a prominent theme in science fiction movies (I most recommend Paycheck, or Eternal Sunshine), a new study circulating in the blogosphere demonstrates one molecular technique for inhibiting long term memory functions. To understand the cognitive effects of this technique, you first need a quick background on memory processes:

Over the long-term, recent memories encoded by the hippocampus are thought to be transitioned into neocortex. This process is often known as consolidation, and can be observed in at least a couple of ways. First, amnesics who have sustained damage to the hippocampus will not only show impairments in forming future memories, but will also show temporally-graded retrograde amnesia - in other words, they are unable to access relatively recent memories as well. Second, sleeping (and even awake) rat hippocampi can be observed "replaying" recent activity patterns, as though interleaving these experiences for a relatively slow-learning neocortex to absorb. In humans, memories are strengthened after a good night's sleep as compared to an equivalent amount of time awake.

What mechanisms support this consolidation process? I've written previously about work from Harvard showing that destruction of the Armitage protein is important for protein synthesis at the synapse. Previous work has also shown that NMDA antagonists can block memory encoding, but not memory maintenance or consolidation. However, new research from SUNY has shown that inhibition of a different molecule - the protein kinease M-Zeta - can selectively disrupt the storage of memories up to 1 day old, but not the encoding of new memories. This disruption of storage is thought to occur by downregulating AMPA receptors in the CA1 region of hippocampus, which function prominently in late LTP.

Does this molecule work by disrupting consolidation processes within a specific time-window, or does it truly erase these memories?

Note: this post has been heavily edited/revised in response to reader comments.

Related Posts:
Molecular Basis of Memory
A role for Protein in Learning and Memory
A Role for MicroRNA in Learning and Memory

3 Comments:

Blogger Joanna said...

I was really surprised to come across a blog post on this article! I actually just read it for a lab meeting presentation that I'm going to give, as I'm currently doing my Masters degree on the role of PKC zeta on synaptic plasticity.

The article really is fascinating, as it's one of the first demonstrations of the role of LTP maintenance in persistent memory storage. You have some of the results wrong, though, as the study does not so much concern consolidation as retention and storage - the PKM zeta inhibitor eliminates long-term stored info while not disrupting recently encoded info. The idea of being able to create "time-selective retrograde amnesia" is a huge leap, the study essentially states that PKM zeta is needed to maintain long-term memories. It was still great to see this article referenced, always fun to run across my niche on the blogosphere!

And btw - Eternal Sunshine of the Spotless mind was "inspired" by the research of Karim Nader, a prof/researcher in my department!

9/06/2006 05:32:00 PM  
Blogger Chris Chatham said...

Joanna - thanks so much for the heads up. I'd like to discuss this a little bit more with you, to make sure that we have a disagreement of interpretation rather than a disagreement of what the authors found (the "facts" ;). To that end:

The authors showed that STM, but not LTM is impaired by ZIP, which inhibits PKM zeta (on this I think we agree). They also showed that this loss of information was persistent, which is consistent with either a failure of retrieval OR a failure for the memory to have become consolidated. Likewise, when they showed that ZIP affected memories up to 1 month old, this could reflect retrieval failure OR failure of consolidation. Of course, to rule out consolidation completely, they would have to show that even the oldest memories were "erased" by ZIP - which might not actually happen and generally seems hard for me to imagine. Nonetheless, until they demonstrate that the oldest memories were erased as well, ZIP could be interpreted as impairing retrieval OR impairing consolidation ... would you agree?

It's quite possible I'm misunderstanding something or overlooking a relevant finding. Please let me know if so...

Anyway, I agree with you that my hasty attempt at a conclusion for future science fiction novels ("this research establishes a technology surely worthy of future science fiction: the ability to create time-selective retrograde amnesia, without disrupting retrieval processes, or current or future learning") was incorrect - as such I have changed the font to strikeout, to reflect your comment. :)

9/06/2006 06:06:00 PM  
Blogger Joanna said...

Hi Chris, it's great to be having a wee conversation on this really interesting topic!

As for your comments, I think we have both a problem with the facts of the paper and of our interpretations.

First, the facts: the essential and main point of the article is "the ability of ZIP to eliminate long-term stored information, while leaving recently acquired information intact" - ZIP impaires LTM and not STM. Moreover, ZIP reverses late long-term potentiation (LTP) while not affecting early LTP. The correlation between LTM and LTP was one of the points the authors wanted to investigate here, as the entire first part of the paper deals with electrophysiology.

As for interpretation, the whole retention/retrieval/encoding argument is an old and reoccuring one. The authors do tackle it here: "PKM zeta inactivation may disrupt information storage, in which case the effect of ZIP would be persistent, or information retrieval, in which case the effect would be transient". They indeed found the memory impairement caused by ZIP persisted even after the elimination of the inhibitor - it was not a transient effect, and therefore did not disrupt retrieval.

Not everyone would agree, as sometimes it is difficult to empirically distinguish between storage and retrieval (consolidation is also sometimes looked down on; my supervisor has a couple of whole lectures entitled "Why Consolidation is a Bad Word"), but I'm pretty convinced by the evidence.

Hope this clears some things up! :)

9/07/2006 12:37:00 PM  

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