Lost forever or temporarily misplaced? The long debate about the nature of memory impairment - PubMed (original) (raw)
Lost forever or temporarily misplaced? The long debate about the nature of memory impairment
Larry R Squire. Learn Mem. 2006 Sep-Oct.
Abstract
Studies of memory impairment in humans and experimental animals have been fundamental to learning about the organization of memory and its cellular and molecular substrates. When memory impairment occurs, especially after perturbations of the nervous system, the question inevitably arises whether the impairment reflects impaired information storage or impaired accessibility. This topic has been the subject of considerable commentary and experimental work over the years. In this reappraisal, I first consider four broad areas of behavioral study from the 1970s and 1980s that led to a dominant and compelling view of memory impairment as a deficit of information storage. Second, I identify some ambiguities that arise about how the terms "storage" and "retrieval" are applied, especially when the evidence is somewhat indirect and based on a behavioral-psychological level of analysis. I then review neurobiological findings that have been largely overlooked in these discussions. The relevant studies are ones where it has been possible to monitor neurons and synapses in direct relation to behavioral memory, for example, in animals with simple nervous systems and in single cell recordings from behaving monkeys. This work provides a straightforward and illuminating perspective on the question and confirms the view that first emerged from less direct evidence.
Figures
Figure 1
Rats were given inhibitory avoidance training and tested for retention 24 h (T1) and 48 h (T2) after training. Long latencies to respond at retention signify good memory of the training, and short latencies signify poor memory. Rats given strong footshock (strong FS) remembered well at both retention tests, and rats given electroconvulsive shock immediately after strong footshock (strong FS-ECS) were amnesic. A non-contingent footshock given in a different apparatus 1 h after T1 (FSECS+NCFS) markedly improved retention at T2. Importantly, other animals performed about as poorly as the amnesic animals at T1 and T2 by virtue of receiving only a weak footshock at training (weak FS). These animals also markedly improved their retention score at T2 when a non-contingent footshock was given after T1 (weak FS-NCFS). (Adapted from Gold et al. 1973).
Figure 2
Mice were trained for 20 trials on an object discrimination task and were then retested 24 h later by giving 20 trials of reversal training (the object that was previously incorrect was now correct). During initial training, normal animals achieved a score of 7.6 trials correct. Reversal performance was easier for mice given cycloheximide before training than for control mice, because the mice given cycloheximide were amnesic for the original task. Mice given cycloheximide before training and amphetamine before the reversal test performed even better. If memory of the original discrimination had recovered, it would have interfered with reversal performance. Thus, amphetamine did not recover memory but facilitated reversal performance independently of the effects of cycloheximide. The drugs indicated above the bars were given 30 min before training. The drugs indicated below the bars were given 1 h before retest. SAL indicates saline; CXM, cycloheximide; dAMP, d-amphetamine. Brackets show SEM. (Adapted from Squire 1979).
Figure 3
The physiological and structural changes associated with long-term behavioral modification in Aplysia were established in cultures of sensory neurons and the gill motor neuron L7. These neurons are components of the reflex circuit for long-term sensitization. Applications of serotonin enhanced the physiological efficacy of the sensorimotor synapse 24 h after treatment and increased the number of sensory neuron varicosities making contact with neuron L7 (black bars). Varicosities are structural features on neurites that identify synaptic contacts. Addition of inhibitors of protein synthesis (gray bars) or RNA synthesis (white bars) 1 h before application of serotonin blocked both the physiological and the structural changes. For the physiological change, the bars show the change in the amplitude of the excitatory post-synaptic potential (EPSPs) in neuron L7 24 h after serotonin. Brackets show SEM. (Adapted with permission from Cell Press © 1992, Bailey et al. 1992.)
Figure 4
Neuronal activity in neocortex and long-term declarative memory. Monkeys learned 12 pairs of visual patterns (1 and 1′, 2 and 2′, and so on). (A) The gray bars show the response of a neuron in inferotemporal cortex to each of the 12 cue patterns, and the black bars show the firing rate to each pattern's learned associate. This neuron fired to both patterns 5 and 5′. Because the pairings were arbitrary, this result shows that the neuron has “learned” the pairings. (B) After lesions of perirhinal and entorhinal cortex, neurons still exhibited selective responding to the patterns (this neuron fired to patterns 7 and 9), but the neurons no longer coded pair associations. (C) The correlation coefficient shows the relationship between a neuron's response to each pattern and its paired associate. Neurons were recorded either before the lesion (white bar, n = 92), after the lesion using the same patterns (gray bar, n = 72), or after the lesion with a new set of patterns (black bar, n = 75). Brackets show SEM. (A) (Adapted with permission from Nature © 1991, Sakai and Miyashita 1991; (B,C) adapted with permission from National Academy of Sciences, U.S.A. © 1996, Higuchi and Miyashita 1996).
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References
- Anderson MC, Bjork RA, Bjork EL. Remembering can cause forgetting: Retrieval dynamics in long-term memory. J. Exp. Psychol. Learn. Mem. Cogn. 1994;20:1063–1087. - PubMed
- Bailey CH, Montarolo P, Chen M, Kandel ER, Schacher S. Inhibitors of protein and RNA synthesis block structural changes that accompany long-term heterosynaptic plasticity in Aplysia. Neuron. 1992;9:749–758. - PubMed
- Bayley PJ, Hopkins RO, Squire LR. Successful recollection of remote autobiographical memories by amnesic patients with medial temporal lobe lesions. Neuron. 2003;37:135–144. - PubMed
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