Wednesday, April 8, 2009

PKMzeta and Long-Term Memory

Just a few days ago the New York Times featured an article in their Brain Power series that has quickly risen to the top of their "Most E-Mailed" list: "Brain Researchers Open Door to Editing Memory". The article discusses some recent breakthroughs by Shema, Hazvi, Sacktor, and Dudai in their research on the molecular basis for long-term memory, recently published in the journal Learning & Memory under the title "Boundary conditions for the maintenance of memory by PKMzeta in neocortex". The subject of their work is the molecule PKMzeta, a protein found in regions of the brain that are involved with long-term memory. Their work also centers around the molecule ZIP and its ability to inhibit PKMzeta, and thereby "erase" long term memories.

As the authors note in their introduction, protein kinase molecules such as PKMzeta have been under investigation for some time in terms of their role in brain function, specifically with regard to learning and memory. Only recently has PKMzeta been isolated in certain studies for its role in sustaining long-term memory. The study by Shema et al used a variety of training scenarios (with rats as their model organism) designed to form long-term aversions to certain tastes (sugar and salt mixed with water). The researchers then dosed the rats with ZIP, varying the timing of the ZIP dose relative to the training process, as well as the strength of the ZIP dose, in order to determine the limitations on PKMzeta's role in the long-term memory.

The findings indicate that PKMzeta's role in long-term memory formation begins at somewhere around 72 hours after the training event, and that the molecule's role in sustaining the long-term memory sustains for at least three months after the training. The researchers demonstrated that PKMzeta is not involved in short-term memory processing, as doses of ZIP given just prior to training, during training, and shortly after training did not affect the formation of long-term memory. Furthermore, the researchers found that similar long-term memories (taste aversion) could be re-formed after rats were dosed with ZIP. The researchers also found that ZIP dosing has a critical concentration below which it is ineffective, and that its "erasure" of long-term memory is not taste-specific.

Although these findings provide significant insight into the limitations of PKMzeta's role in long-term memory formation and sustainment in the rat neocortex, much more needs to be discovered regarding the specific mechanism of action for the molecule. The researchers note that PKMzeta is involved with pathways involving neurotransmitter receptor expression as well as with cytoskeletal modulation in order to enhance synaptic connection strength, but much more detail is needed in order to understand how these types of changes relate specifically to long-term memory. This also sets aside the ever-present question of how these cellular and molecular changes are experienced consciously.

While it is exciting to see that headway is being made in the molecular basis for learning and memory, and to extrapolate that someday we might be able to help students learn and retain information better through medications and therapies that target these specific pathways, it is also important to keep in mind that there are significant differences between the rat brain and the human brain, and that the limitations of communicating with rats means that only certain types of memory-based behaviors, such as taste aversion, have been studied. It is certainly true that the basis of learning and memory in the human brain will be molecular and cellular in nature, but these specific findings regarding PKMzeta and ZIP may be localized to regions of the brain that are of little interest to human educators. However, these findings clearly indicate that we are increasing our ability to understand the inner workings of the brain, and that it is reasonable to place hope in neuroscience's ability to disentangle the complex mechanisms of learning and memory.


  1. Now, what about people who can erase their own memory from a single thought?

  2. It would make sense that the ability to forget something with selectivity would be explicable as a physiological process just as much as the ability to remember. Thinking about this reminds me of a line from Ani DiFranco's "Dilate": "i forget every time / and the forgetting defines me / that's what defines me".

  3. E' possibile che tale scoperta sia già in fase di applicazione sugli individui? cioè un amico mi ha riferito che dei medici vogliono resettargli la memoria con dei farmaci perchè ritengono che i gravi disturbi fisici (valori ormonali, gh, testosterone, insulina...) di cui soffre e che lo stanno devastando siano dovuti ad un "errore" di informazioni celebrali accaduto nel passato...quindi resettando l'intera memoria tutto dovrebbe riprendere a funzionare in maniera adeguta e questo sulla base di un "test" fatto attraverso il distacco della corteccia celebrale per un tot di giorni che avrebbe dato come risultato il lieve ma evvidente stabilizzarsi dei valori...a me sembra fantascenza è possibile una cosa del genere?anche perchè danno come percentuale di successo il 100% con ovviamente però la predita di qualsiasi ricordo...
    Aspetto con ansia un suo arere

  4. but why hasnt any further testing ben done on humans or apes?