There are two confusing but potentially important papers in the Jan. 25 2013 Science on long-term memory (LTM) formation in fruit flies:
Pierre-Yves Placais & Thomas Preat. To favor survival under food shortage, the brain disables costly memory. 339:440-441.
Yukinori Hirano et al. Fasting launches CRTC to facilitate long-term memory formation in Drosophila. 339:443-446.
These papers categorize long-term memory formation along three axes.
- Aversive vs. appetitive: Actions that the brain interprets as helping it avoid something, vs. actions that help it attain something.
- Fasting-dependent (fLTM) vs. spaced training-dependent (spLTM): fLTM is formed in a single learning episode, but only at the time that an organism first obtains food after a long fast. spLTM does not require fasting but requires repeated training.
- LTM vs. ARM: Memories that require protein synthesis (LTM) vs. "anesthesia-resistent memory" (ARM), which does not. (The papers don't explain what ARM might correspond to in humans.)
The relationship between these is unclear, particularly as each of these three axes is claimed at various times to determine whether memory can be learned in a single training cycle (appetitive, fLTM, and/or ARM) or not (aversive, spLTM, and/or LTM). But these things appear to be likely, or at least to be reasonable hypotheses, if these pathways are conserved in humans:
- How quickly you learn something depends on how much you've eaten recently. You learn most quickly immediately after ending a long fast. Your brain thinks you just learned something that saved it from starvation. (But note that a 1-day fast for a fruit fly could be compared to a human fasting for months.)
- How quickly you learn something depends on whether your brain thinks that this knowledge is to avoid something bad (slow learning) or to attain something good (fast learning).
- Almost all of the mutations that extend lifespan in organisms from yeast to humans impact the FOXO3a vs. mTORc1 axis (to use the human analogs). Expressing FOXO3a inhibits mTORc1 and extends lifespan in various ways; producing and assembling more mTORc1 inhibits FOXO3a and promotes protein synthesis, growth, reproduction, tissue repair, and immune response. We already know that extending lifespan, in general, is antithetical to building muscle. It may also be antithetical to forming long-term memories. This makes sense.
- Learning rate can be increased by expressing or inhibiting proteins involved in these responses. Hirano et al. focus on activating a cAMP-regulated transcriptional coactivator (CRTC) by dephosphorylating it in order to invoke fLTM. They were able to do this and enable flies to learn quickly without fasting followed by feeding.
I'd really appreciate it if somebody would do a literature review and a comparison of the pathways involved to those in humans, and summarize their findings.