Protein synthesis with learning

SW VandeCarr

It's been known for some time that synapses are strengthened during the brain's processing of new information. This includes passive activities such as listening to music. However, the linked article discusses new research that indicates the RNA linked protein synthesis that occurs with synapse strengthening is repressed by other proteins. So the learning process is actually initiated by derepression. The repressive proteins must be degraded for the active proteins to be synthesized. What might happen if we were able to block the synthesis of repressive proteins so that synapse strengthening could occur all the time or perhaps selectively as when, for instance. we need study for an exam?

http://www.physorg.com/news180780161.html

EDIT: In case you're wondering about "RNA linked protein synthesis" (since tRNA and mRNA is involved in all protein synthesis), I believe the article is referring to non-coding RNA which plays a role in memory formation.

http://physrev.physiology.org/cgi/content/full/87/3/799.

atyy

Hopefully free in 6 months from Pubmed

http://www.cell.com/neuron/abstract/...2809%2900939-8

A Coordinated Local Translational Control Point at the Synapse Involving Relief from Silencing and MOV10 Degradation

Sourav Banerjee, Pierre Neveu, and Kenneth S. Kosik

Persistent changes in synaptic strength are locally regulated by both protein degradation and synthesis; however, the coordination of these opposing limbs is poorly understood. Here, we found that the RISC protein MOV10 was present at synapses and was rapidly degraded by the proteasome in an NMDA-receptor-mediated activity-dependent manner. We designed a translational trap to capture those mRNAs whose spatiotemporal translation is regulated by MOV10. When MOV10 was suppressed, a set of mRNAs—including α-CaMKII, Limk1, and the depalmitoylating enzyme lysophospholipase1 (Lypla1)—selectively entered the polysome compartment. We also observed that Lypla1 mRNA is associated with the brain-enriched microRNA miR-138. Using a photoconvertible translation reporter, Kaede, we analyzed the activity-dependent protein synthesis driven by Lypla1 and α-CaMKII 3′UTRs. We established this protein synthesis to be MOV10 and proteasome dependent. These results suggest a unifying picture of a local translational regulatory mechanism during synaptic plasticity.

atyy

If it's downstream of NMDA, and NMDA is what limits strengthening to synapses that "fire together, wire together", then by bypassing that specificity, wouldn't you get strengthening of all synapses, whereas I'd imagine you only want specific synapses strengthened for an exam?

SW VandeCarr

Thanks for the link atty. I'll be interested in reading the article when its free, or when I can get to a medical library.

Since different synapses in different parts or the brain are somewhat specialized (different neurotransmitters for example), I think any drug will have effects at least limited to those synapses involved in memory and learning. First suppose you took such a drug all the time. Do all the relevant synapses just keep getting stronger or will some kind of tachyphylaxis occur? Would it cause seizures, hallucinations, hyperactivity or other severe adverse effects through overstimulation? Obviously such a drug would be heavily tested in other mammalian models before being very carefully introduced into human subjects.

But suppose intermittent use proved safe and effective? Would this be a good or bad thing for individuals and society in general. I can see it's possible therapeutic use in those with learning disabilities. However, as an aid to memory for enhancement purposes only, I might be concerned. Would this be something like athletes taking performance enhancing drugs?

atyy

Well, if it's safe and effective, then the questions are as you mentioned - no or little reservation for therapeutic use, some concern over "abuse". I myself don't find any ethical problem with performance enhancing drugs a priori - in practice they are often not safe, and they are cheating because they break the rules of the game - but there are safe drugs such as caffeine that are permitted by sports rules, and I don't object.

A free article that covers some potential drugs - see his comments on "neuromodulators" - however the review is more general than that and includes potential behavioural strategies http://www.utdallas.edu/~kilgard/Moucha_Review.pdf

SW VandeCarr

Yes, its a good review, but anyone following neuroscience needs to read the more recent literature. It's a very active field of research.

Eric McClean

Thanks for sharing this with us.

atyy

What do you have in mind? I thought advances in memory erasure were pretty interesting, but I think you'd like something that does the opposite?

http://dx.doi.org/10.1016/j.neuron.2008.08.027
http://www.sciencemag.org/cgi/conten.../325/5945/1258

BTW, why not just have open book, open note exams, then memorizing will become (approximately) irrelevant?

SW VandeCarr

At my age, I'm not that interested in memory erasure. However the second abstract (N Gogolla et al) on perineuronal nets (PNNs)is interesting. It makes me wonder how fear memories are encoded and identified. The mechanism must be very old phylogenetically, residing in the limbic system with later connections to the neocortex in mammals. It makes sense that post natal animals would not be protected from erasure since fear memories might interfere with other learning and nature freely sacrifices the young in natural selection. Therefore it probably doesn't matter that the young animal can't remember to stay away from danger. (Life is cruel.)

Open book? Memorizing irrelevant? Do you want your doctor to have gotten through medical school that way?