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Integration of New Information Goes Beyond State Dependency
Submit responseAs indicated in the title of our paper, we proposed that retrograde amnesia results from the integration of new information with an inital memory (see also Gisquet-Verrier and Riccio, 2012). It is true that in our experiments, the integration hypothesis merges with state dependency. But our view is more general : When the impairment results from another source, such as an interpolated learning episode, the integration hypothesis states that the impairment is due to the integration of the new information with the previous learning (Hupbach et al., 2007). Under these conditions integration causes interference and not state dependency. The case of post-reactivation extinction (Monfils et al., 2009 ; Schiller et al., 2010) mentioned by Nader and Haubrich is particularly illustrative. In these studies, delivering extinction after the memory reactivation, permanently attenuates the fear memory, an effect not obtained when extinction occurred without a prior reactivation. According to our integration hypothesis, the new information : "the CS is not dangerous", was integrated into the reactivated fear memory, resulting in a memory trace of the CS with a neutral hedonic value. Such "emotional remodeling", which is a consequence of our integration hypothesis, contitutes a new therapeutic approach currently being explored (see Toledano and Gisquet- Verrier, 2013 and Chopin et al., 2015, for emotional remodeling attempts in rats and in humans).
Nader and Haubrich further argue that reconsolidation impairment is defined as intact post-reactivation short-term memory and impaired post- reactivation long term-memory (Nader and Hardt, 2009). The fact that memory remains intact shortly after amnesic treatment assumes a separate short term memory not disrupted by the treatment. Alternatively, as we proposed, if the disruption of performance results from the integration of the amnesic drug cues, good retention performance should be obtained as long those contextual cues are present and perceived. Such a position offers a convincing and simple explanation for a preserved short term memory.
Contrary to state dependency the memory integration view can also account for cases of memory enhancements. Typically, these treatments (e.g., strychnine, amphetamine...), increase arousal and attention. Administered while the memory is in an active state, these effects would be integrated with the initial memory, strengthening the value of the intial reinforcer and thus improving the subsequent retention performance. It is important to consider that treatments leading to opposite effects do not necessarily rely on opposite processes. Here we propose that treatments disrupting and enhancing memory may both result from the same process : The integration of new information in an active and malleable memory trace can have opposite consequences.
Finally, we are well aware that the latency measure, as well as freezing, used by the commenters lab and many others, could potentially be distorted by such artificial variables as "sleep","illness" or "death". However, we included adequate control groups to evaluate any direct effects of the drugs on performance and we have ensured that our data were based on fully mobile rats.
References
Chopin M.V. et al. Cocaine use disorder treated with specific cognitive behavioral therapy and adjunctive propranolol. Psychotherapy and Psychosomatics (in Press).
Gisquet-Verrier, P. et al. Integration of New Information with Active Memory Accounts for Retrograde Amnesia: A Challenge to the Consolidation/Reconsolidation Hypothesis? Journal of Neuroscience 35, 11623-11633 (2015).
Gisquet-Verrier P., Riccio D.C. Memory reactivation effects independent of reconsolidation. Learn Mem 19(9):401-9 (2012).
Hupbach A. et al. Reconsolidation of episodic memories: a subtle reminder triggers integration of new information. Learn Mem 14:47-53 (2007).
Monfils MH, et al. Extinction-reconsolidation boundaries: key to persistent attenuation of fear memories. Science 324 (5929):951-5 (2009).
Nader, K., Hardt, O. A single standard for memory: the case for reconsolidation. Nat Rev Neurosci 10, 224-34 (2009).
Conflict of Interest:
None declared
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Ou est le foie gras?
Submit responseGisquet-Verrier, et al. (2015) propose that previous reports of consolidation and reconsolidation impairments are due to State Dependent Learning (SD) rather than a storage deficit. SD is an interesting memory effect that may account for some cases of learning. However, we feel that the hypothesis is forced when applied to all cases of amnesia. It is hard to imagine which State would arise during memory update procedures with behavioral interference such as Tetris (Holmes et al., 2009) and post-reactivation Extinction (Schiller et al., 2010) or State constant knockout mice (Bozon et al. 2003)
There is no evidence from these data to support reconsolidation impairment. This is defined as intact post-reactivation short-term memory and impaired post-reactivation long term-memory (Nader & Hardt, 2009). The authors measure response latency using inhibitory avoidance, which could be high if animals avoid the shocked-context (fear). Additional confounds, such as sleeping, illness and death, likely also account for these animals successful on the measure.
Another theoretical shortcoming is that SD is a process that only predicts memory impairments. If the State is present, performance is 100% and if the State is absent performance is 0. Theoretically, it cannot predict or explain any case of memory enhancements as has been found for consolidation, reconsolidation (Tronson et al., 2006), and LTM maintenance (Shema et al., 2011). These memory phases have neurobiological models describing the mechanisms mediating amnesia, which predict which compounds would prevent amnesia from occurring. The AMPA receptor endocytosis blocker Glur23y (Brebner et al., 2005) can prevent amnesia induced by the PKM?? zeta inhibitory peptide ZIP (Migues et al., 2010) or post-reactivation anisomycin (Hong et al., 2013). SD predicts a larger impairment for groups that received multiple drugs because the State should increase in these groups, opposed to the prevention of amnesia reported in literature. Thus, for these reasons SD cannot explain the data of consolidation, reconsolidation and memory maintenance.
References
Bozon, B., Davis, S., Laroche, S. A requirement for the immediate early gene zif268 in reconsolidation of recognition memory after retrieval. Neuron 40, 695-701 (2003).
Brebner, K. et al. Nucleus accumbens long-term depression and the expression of behavioral sensitization. Science 310, 1340-3 (2005).
Gisquet-Verrier, P. et al. Integration of New Information with Active Memory Accounts for Retrograde Amnesia: A Challenge to the Consolidation/Reconsolidation Hypothesis? Journal of Neuroscience 35, 11623-11633 (2015).
Holmes, E.A., James, E.L., Coode-Bate, T., Deeprose, C. Can playing the computer game "Tetris" reduce the build-up of flashbacks for trauma? A proposal from cognitive science. PLoS One 4, e4153 (2009).
Hong, I. et al. AMPA receptor exchange underlies transient memory destabilization on retrieval. PNAS Proceedings of the National Academy of Sciences of the United States of America 110, 8218-8223 (2013).
Migues, P.V. et al. PKMzeta maintains memories by regulating GluR2-dependent AMPA receptor trafficking. Nat Neurosci 13, 630-4 (2010).
Nader, K., Hardt, O. A single standard for memory: the case for reconsolidation. Nat Rev Neurosci 10, 224-34 (2009).
Schiller, D. et al. Preventing the return of fear in humans using reconsolidation update mechanisms. Nature 463, 49-53 (2010).
Shema, R. et al. Enhancement of consolidated long-term memory by overexpression of protein kinaseMz in the neocortex. Science 1207-1210 (2011).
Tronson, N.C., Wiseman, S.L., Olausson, P., Taylor, J.R. Bidirectional behavioral plasticity of memory reconsolidation depends on amygdalar protein kinase A. Nat Neurosci 9, 167-169 (2006).
Conflict of Interest:
None declared
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