Oliver Hardt

A single standard for memory: the case for reconsolidation

Consolidated memories can re-enter states of transient instability following reactivation, from which they must again stabilize in order to persist, contradicting the previously dominant view that memory and its associated plasticity mechanisms progressively and irreversibly decline with time. We witness exciting times, as neuroscience begins embracing a position, long-held in cognitive psychology, that recognizes memory as a principally dynamic process. In light of remaining controversy, we here establish that the same operational definitions and types of evidence underpin the deduction of both reconsolidation and consolidation, thus validating the extrapolation that post-retrieval memory plasticity reflects processes akin to those that stabilized the memory following acquisition.

PKMζ maintains memories by regulating GluR2-dependent AMPA receptor trafficking

The maintenance of long-term memory in hippocampus, neocortex and amygdala requires the persistent action of the atypical protein kinase C isoform, protein kinase Mζ (PKMζ). We found that inactivating PKMζ in the amygdala impaired fear memory in rats and that the extent of the impairment was positively correlated with a decrease in postsynaptic GluR2. Blocking the GluR2-dependent removal of postsynaptic AMPA receptors abolished the behavioral impairment caused by PKMζ inhibition and the associated decrease in postsynaptic GluR2 expression, which correlated with performance. Similarly, blocking this pathway for removal of GluR2-containing receptors from postsynaptic sites in amygdala slices prevented the reversal of long-term potentiation caused by inactivating PKMζ. Similar behavioral results were obtained in the hippocampus for unreinforced recognition memory of object location. Together, these findings indicate that PKMζ maintains long-term memory by regulating the trafficking of GluR2-containing AMPA receptors, the postsynaptic expression of which directly predicts memory retention.

The dynamics of memory: Context-dependent updating

Understanding the dynamics of memory change is one of the current challenges facing cognitive neuroscience. Recent animal work on memory reconsolidation shows that memories can be altered long after acquisition. When reactivated, memories can be modified and require a restabilization (reconsolidation) process. We recently extended this finding to human episodic memory by showing that memory reactivation mediates the incorporation of new information into existing memory. Here we show that the spatial context plays a unique role for this type of memory updating: Being in the same spatial context during original and new learning is both necessary and sufficient for the incorporation of new information into existing episodic memories. Memories are automatically reactivated when subjects return to an original learning context, where updating by incorporating new contents can occur. However, when in a novel context, updating of existing memories does not occur, and a new episodic memory is created instead.

Decay happens: the role of active forgetting in memory

Although the biological bases of forgetting remain obscure, the consensus among cognitive psychologists emphasizes interference processes, rejecting decay in accounting for memory loss. In contrast to this view, recent advances in understanding the neurobiology of long-term memory maintenance lead us to propose that a brain-wide well-regulated decay process, occurring mostly during sleep, systematically removes selected memories. Down-regulation of this decay process can increase the life expectancy of a memory and may eventually prevent its loss. Memory interference usually occurs during certain active processing phases, such as encoding and retrieval, and will be stronger in brain areas with minimal sensory integration and less pattern separation. In areas with efficient pattern separation, such as the hippocampus, interference-driven forgetting will be minimal, and, consequently, decay will cause most forgetting.

The spatial brain

Themes emerging from the collection of articles in the Special Section on Long-Term Spatial Memory include the notion of multiple spatial systems, the relation between spatial representations and episodic memory, the role of context, and the neural systems involved in space. The authors conclude that distinguishing between egocentric and allocentric spatial systems makes sense of both behavioral and neurobiological data. The special role of the hippocampal system in allocentric space, and as a consequence, in context, suggests how a spatial system might end up central to the ability to remember episodes.

Update on Memory Systems and Processes

Ideas about how the brain organizes learning and memory have been evolving in recent years, with potentially important ramifications. We review traditional thinking about learning and memory and consider more closely emerging trends from both human and animal research that could lead to profound shifts in how we understand the neural basis of memory.

PKMζ maintains 1-day- and 6-day-old long-term object location but not object identity memory in dorsal hippocampus

Continuous activity of the atypical protein kinase C isoform M zeta (PKMζ) is necessary for maintaining long‐term memory acquired in aversively or appetitively motivated associative learning tasks, such as active avoidance, aversive taste conditioning, auditory and contextual fear conditioning, radial arm maze, and watermaze. Whether unreinforced, nonassociative memory will also require PKMζ for long‐term maintenance is not known. Using recognition memory for object location and object identity, we found that inactivating PKMζ in dorsal hippocampus abolishes 1‐day and 6‐day‐old long‐term recognition memory for object location, while recognition memory for object identity was not affected by this treatment. Memory for object location persisted for no more than 35 days after training. These results suggest that the dorsal hippocampus mediates long‐term memory for where, but not what things have been encountered, and that PKMζ maintains this type of spatial knowledge as long as the memory exists.

Storage or Retrieval Deficit: The Yin and Yang of Amnesia.

To this day, it remains unresolved whether experimental amnesia reflects failed memory storage or the inability to retrieve otherwise intact memory. Methodological as well as conceptual reasons prevented deciding between these two alternatives: The absence of recovery from amnesia is typically taken as supporting storage impairment interpretations; however, this absence of recovery does not positively demonstrate nonexistence of memory, allowing for alternative interpretations of amnesia as impairment of memory retrieval. To address this shortcoming, we present a novel approach to study the nature of amnesia that makes positive, i.e., falsifiable, predictions for the absence of memory. Applying this paradigm, we demonstrate here that infusing anisomycin into the dorsal hippocampus induces amnesia by impairing memory storage, not retrieval.

A case of psychogenic fugue: I understand, aber ich verstehe nichts

Psychogenic fugue is a disorder of memory that occurs following emotional or psychological trauma and results in a loss of ones personal past including personal identity. This paper reports a case of psychogenic fugue in which the individual lost access not only to his autobiographical memories but also to his native German language. A series of experiments compared his performance on a variety of memory and language tests to several groups of control participants including German-English bilinguals who performed the tasks normally or simulated amnesia for the German language. Neuropsychological, behavioral, electrophysiological and functional neuroimaging tests converged on the conclusion that this individual suffered an episode of psychogenic fugue, during which he lost explicit knowledge of his personal past and his native language. At the same time, he appeared to retain implicit knowledge of autobiographical facts and of the semantic or associative structure of the German language. The patients poor performance on tests of executive control and reduced activation of frontal compared to parietal brain regions during lexical decision were suggestive of reduced frontal function, consistent with models of psychogenic fugue proposed by Kopelman and Markovitsch.

Response to Alberini: right answer, wrong question

In a recent TINS review, Cristina Alberini made many interesting points concerning the relationship between consolidation and reconsolidation [1]. One of the main arguments advanced is that reconsolidation is not an exact copy of consolidation. For example, the transcription factor CCAAT-enhancer-binding protein β (C/EBPβ) is involved in consolidation of inhibitory avoidance but not in reconsolidation in the hippocampus [2]. The author reported numerous other clear demonstrations that the mechanisms mediating reconsolidation are not identical to the processes involved in the initial consolidation of memory [1].