Reconsolidation Of Memories

What if every time you recalled a memory you made that memory subject to erasure? A frightening thought, certainly. The idea also seems somewhat at odds with our perception of consistency in our own memories—recalling them seems to make them stronger, not weaker. Nevertheless, recent provocative studies have suggested that every time we recall a specific memory, we make it necessary for that memory to be reestablished. The word used to describe this attribute of memory is "reconsolidation" in reference to the well-known attribute that long-term memories, when initially formed, are labile and subject to disruption over a period of hours (see text). It appears that previously established long-term memories also are subject to disruption specifically during that period immediately after each time they are recollected.

The most definitive recent experiment concerning memory reconsolidation was performed by Karim Nader and Glenn Schafe in Joe LeDoux's lab (30), although important work in this area has also been performed by the laboratories of Susan Sara, Yadin Dudai, and Alcino Silva, among others. Nader et al. (30) studied memory reconsolidation using cued fear conditioning in rats, which as we discussed in Chapter 2 is an amygdala-dependent process. Basically, Nader et al. found that when an animal is reexposed to a conditioned stimulus (an auditory cue in this case), which of course elicits recollection of a prior CS-US pairing, restorage of that memory can be disrupted by inhibiting protein synthesis in the amygdala. The same memory is impervious to an equivalent period of protein synthesis inhibition as long as the animal is not stimulated to recall the CS-US pairing during that time. The implication of these studies is that reactivated memories must be put back into long-term storage via a protein synthesis-dependent process similar to that used during the initial consolidation period. Hence the term "reconsolidation."

There are, of course, a great number of questions raised by these studies. Is the reconsolidation mechanism identical to the initial consolidation mechanism? Are all long-term memories subject to reconsolidation after each recollection, or is this mechanism restricted to particular brain areas or memory types? Might disruption of this process contribute to memory pathologies such as aging-related memory loss? Could pharmacologic means be used as a therapeutic intervention in "pathologic" memory such as post-traumatic stress disorder? Future studies will hopefully lead to new insights into these and other questions concerning this fascinating phenomenon.

of animal lesion studies and indeed with the memory consolidation deficits of other patients with more selective hippocampal lesions. However, it is important to remember that H.M. has lesions of the surrounding perihippocampal cortices and the amygdala, which likely contribute to the particularly pronounced nature of his deficits (Figure 16).

Also, given what we discussed earlier in this chapter about the role of the hippocampus in multimodal cognitive processing,

Radiant Thinking

FIGURE 16 MRI of H.M.'s brain lesions. The diagram on the left shows Patient H.M.'s lesions as estimated by the surgeon who performed the original operation (2). The diagram on the right, shows Patient H.M.'s actual lesions as shown by magnetic resonance imaging (MRI). A through D in both diagrams are drawings of coronal sections from rostral (A) to caudal (D). In each cross-section (A-D), the right half of the brain is drawn as normal, for purposes of comparison. Figure and MRI data reproduced with permission from Corkin et al. (29).

FIGURE 16 MRI of H.M.'s brain lesions. The diagram on the left shows Patient H.M.'s lesions as estimated by the surgeon who performed the original operation (2). The diagram on the right, shows Patient H.M.'s actual lesions as shown by magnetic resonance imaging (MRI). A through D in both diagrams are drawings of coronal sections from rostral (A) to caudal (D). In each cross-section (A-D), the right half of the brain is drawn as normal, for purposes of comparison. Figure and MRI data reproduced with permission from Corkin et al. (29).

one wonders about generalized cognitive deficits in H.M. as well. I am not referring to a loss of intelligence but rather to the possibility of a general inability to process information about his surroundings, correlations among items and events, and the like. These problems may contribute to his cognitive problems and his long-term memory deficits as well. I should make it clear that I don't believe these considerations negate the conclusion of a deficit in memory consolidation in H.M., but I am simply pointing out that interpreting the basis of H.M.'s cognitive deficits should take into consideration modern ideas about the important role of the hippocampus in information processing as well as memory consolidation.

The role of the hippocampus in memory consolidation that was identified in the seminal studies of H.M. have been confirmed and extended in a wide variety of hippocampal lesion studies in experimental animals. Obviously animal experimentation allows a much more detailed and controlled experimental approach than human studies and a number of attributes of hippocampus-dependent memory consolidation have become clear. For example, inhibitors of protein synthesis block memory consolidation when they are applied after training. Consolidation is known to be a process that occurs over several hours after training. Hippocampus-dependent long-term memory consolidation is also dependent on altered gene expression. Activation of the N-methyl-D-aspartate subtype of glutamate receptor is involved, as are a number of signal transduction mechanisms and neu-romodulatory neurotransmitter systems. Overall, a quite wide variety of studies using many different approaches have demonstrated that involvement in memory consolidation is a central attribute of hippocampal function. We will spend much of the rest of the book discussing the cellular and molecular particulars of this process. In brief, the hippocampus, in addition to its information processing role, serves as a short-term memory store that ultimately downloads information to the cortex for longer-term storage.

The basis for this process is mysterious, but one thing that is clear is that the hippocampus must be able to hold a memory trace for some appreciable period of time—hours to days or weeks at least.

In the next chapter, we will talk about a cellular mechanism likely to be critical to allowing the hippocampus to serve as this sort of memory buffer—long-term potentia-tion (LTP). Long-lasting synaptic poten-tiation of this sort also likely is involved in the precise formation and maintenance of hippocampal place cell firing patterns. We also will touch on shorter-lasting forms of synaptic plasticity that may be involved in short-term storage of information and information processing in the hippocampus as well as phenomena such as post-tetanic potentiation (PTP) and short-term potentia-tion (STP) that may be involved in the "time" aspect of hippocampal processing of CS-US contingencies over the period of a few seconds.

In Chapter 5, we will talk about complex mechanisms regulating the induction of LTP, specifically ending up with examples of how lasting plastic change in hippocam-

pal neurons can be triggered dependent upon three-way or four-way contingencies. These latter examples are the types of cellular mechanisms that are likely to allow the multimodal sensory integration observed in the studies by Eichenbaum's group that we discussed in this chapter.

After we go through the physiology, we then will proceed to the molecules that allow these sophisticated cellular processes to occur. These will be the issues of Chapters 6, 7, and 8.

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Responses

  • gaetano
    Who developed the theory of memory reconsolidation?
    8 months ago

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