Update on memory systems and processes

Abstract

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.

Figure 1

Regions involved in episodic memory. (a) Brain areas important for human episodic memory. (b) Selection of known uni- and bidirectional connections between the major regions of the medial temporal lobe memory system. Figure adapted from Aggleton and Brown (1999) and Bird and Burgess (2008).

Figure 2

Two prominent theories of how long-term episodic memory might be organized are illustrated. As with most models, these assume that episodic memory draws on representations distributed across many specialized processing areas, and that the hippocampus serves to link and bind areas that have insufficient connectivity at the time of memory formation. (a) Acquisition. The sensory areas processing incoming sensory signals are also the site of storage—in these models, perception and memory are not clearly different. Owing to sparse direct connections between the various brain regions involved in processing and representing the current event, the hippocampus serves to indirectly link them. The hippocampus seems particularly suited to provide this function because: (1) its peculiar architecture features an autoassociative network in subfield CA3 that permits the rapid formation of arbitrary associations required to encode events in one trial. This network can drive attractor states (eg, Wills et al, 2005) that accomplish pattern completion, which is an essential ability for memory recall; (2) it is positioned at the highest level of association cortex, receiving heavily processed signals from all the sensory processing areas, as well as other cortical and subcortical structures (cf Felleman and Van Essen, 1991); (3) it has direct and indirect afferent and efferent connections with most of the neocortex (cf Squire et al, 1989); and lastly, (4) it computes cognitive maps that represent allocentric knowledge (O'Keefe and Nadel, 1978), providing a ‘scaffold' to encode sensory experiences within the spatial context of occurrence, thereby critically providing the spatial signature that characterizes event memory (Tulving, 2002a). (b and c) Re-activation of hippocampal traces (which may occur during sleep, for example, Wilson and McNaughton, 1994), leads to co-re-activation of the not yet fully linked neocortical processing areas, which in turn promotes creation of direct links (green lines) between them, or the strengthening of pre-existing sparse connections that initially are not sufficient to support memory. The standard systems consolidation model (SCM) and multiple trace theory (MTT) differ with regard to the involvement of the hippocampus in memory over time. According to SCM (b), initially hippocampal-dependent episodic memories become independent of the hippocampus, owing to the establishment of direct neocortical links between the elements that constitute memory for an event; the state of the hippocampal trace is unclear, as it is either lost or continues to exist even though no longer essential to memory retrieval. The model accounts for the fact that recent memories are more susceptible to hippocampal damage than remote ones by assuming that only when systems consolidation is complete can neocortical circuits faithfully carry out the binding functions of the hippocampus. On the other hand, MTT (c) argues that the hippocampus is always involved in the retrieval of an episodic memory, as only the hippocampus can represent spatial context, and hence only the hippocampus can provide linkages to all the details making up a fully elaborated episode memory. Damage to the hippocampal formation will thus result in a flat temporal gradient of retrograde amnesia—even remote event memories cannot be recalled in their entirety (eg, Lehmann et al, 2007). MTT assumes that each time a memory is re-activated, the hippocampal trace that supports it is expanded and hence strengthened. It is argued that such trace expansion permits the addition of new content to existing memories (new nodes and connections in red).

Figure 3

Infusing protein-synthesis inhibitors into dorsal hippocampus after re-activating contextual fear memories that no longer required the hippocampus for expression resulted in the loss of contextual fear (Debiec et al, 2002). Several explanations of this effect are illustrated. (a) Memory representation according to multiple trace theory (MTT) before memory re-activation. The contextual fear memory consists of components distributed across the neocortex and the medial temporal lobe, including the hippocampus. (b) Recalling this type of memory may lead to plasticity in all re-activated areas. Impairing hippocampal function at this point can lead to several outcomes: (c) Atypical input from an impaired hippocampus may disrupt re-stabilization of re-activated memories in areas receiving input from the hippocampus, so that the entire complex of representations is affected and degraded. (d) The intervention may only affect the hippocampus, leaving representations in other brain areas intact. However, the removal of the hippocampal component results in an inability to retrieve the memory, as crucial information with regard to the spatial context in which the event took place is lost. (e) The hippocampal representation remains, but is decoupled from brain areas representing other aspects of the memory, leading to a lack of fear.

Figure 4

Some paradigms to study episodic-like memory in rats. (a) Rats are attracted to novelty. In order to recognize novelty, they must have knowledge of familiarity, that is, memory for what they have encountered in the past. This is the logic behind novel object preference-based object recognition paradigms. First (t1), rats are exposed to two identical copies of an object (‘A'). As both of these objects are identical and thus equally new, rats tend to spend about the same amount of time exploring each. Varying the amount of exposure moderates how long memory for these objects may last. Later (t2), rats are exposed to either an old or a new object (replacing one copy of one old object at its original location), or they are exposed to the same objects as during sampling (t1), but with one object moved to a new location. If rats have memory for the old objects and their locations at t2, they will explore the novel object, or the old object in a new location, more so than the familiar object or familiar location. These paradigms have the advantage that no extrinsic motivation needs to be supplied to provoke the behavior of interest. However, if needed, an emotional component can be easily included, which will permit the study of the effect of positive and negative affect on memory organization and persistence within this paradigm. (b) A recently developed paradigm (Easton and Eacott, 2009) based on the novel object preference to study memory for what–where–when (see text for explanation, section ‘The MTL, recollection and familiarity'). (c) Another episodic-like task exploiting novel object preference (Kart-Teke et al, 2006). During sampling (t1), rats are exposed to four identical copies of an object, and at (t2), they are presented with four new objects. Some objects during t2 are at positions that have been occupied by an object during t1, and vice versa. Finally, during the test (t3), rats are presented with two objects from t1 and two from t2. Two of the objects are at their original positions (A1 and B1), and two are at positions that have been previously occupied by objects: one object from phase t1 (A2) is at a location where an object B had been placed during phase t2, and one object from phase t2 (B2) has been placed at the location occupied by an A object during phase t1. Thus, during the test phase (t3) rats are confronted with varying degrees of novelty—the B objects from phase t2 had been more recently experienced than the A objects from phase t1, and thus the A objects should attract more exploratory activity. However, some objects are at new locations. If rats possess episodic-like knowledge of what–when–where, they should explore the misplaced objects (A2, B2) more than those at their original location (A1, B1).