Memories initially processed in the hippocampus are transferred to the for long-term storage

Long-Term Potentiation, Synaptic Tagging, and the Consolidation Model of Memory

The consolidation hypothesis of memory was first proposed by Müller and Pilzecker in 1900.157 They noted that memory for new information could be disrupted by learning other information shortly after the initial training. This effect, calledretroactive interference, is temporally graded such that the susceptibility of the memory is greatest immediately after learning and decreases with time. Müller and Pilzecker proposed that the memory trace must initially exist in a fragile state, but subsequently becomes stable through the process ofconsolidation. The consolidation hypothesis remains the framework for understanding the temporal course of memory processes and behavior.

For a memory trace to be consolidated, it must of course be created. The term used to describe this process isencoding. Encoding implies that the networks mediating the neural representation of an event as it is experienced do not immediately return to their previous state and are modified in such a way that potentiates reactivation of that representation. Thesynaptic plasticity and memory hypothesis states that activity-induced synaptic plasticity is both necessary and sufficient for the information storage underlying memory,158 and within this framework encoding implies that some form of synaptic plasticity has been initiated. However, encoding cannot in itself assure the propagation of a memory trace. Encoding creates the potential for the formation of a long-term memory.

The minimal events that constitute the neural correlates of encoding are incompletely understood. Cellular models demonstrate that functional changes in synaptic strength can occur in the absence of any structural change in dendritic spines.159 The perpetuation of these initial changes through structural and functional remodeling represents the neural correlate of memory consolidation. The prevailing cellular model for this is LTP,160 which describes a durable increase in synaptic transmission efficiency following a stimulation protocol. It is now recognized that LTP occurs richly throughout the hippocampus, as well as in other afferent pathways.161 LTP can be induced by nonphysiologic high-frequency stimulation, but also by stimulation protocols that resemble physiologic activity, the most important being bursts in the theta range (4-8 Hz).162 This is of notable relevance to memory, as synchronized hippocampal theta oscillations appear critical to successful memory behaviors.134

The breadth and depth of literature on the mechanisms of LTP are far too voluminous to summarize here. Nonetheless, certain principles are essential and relevant to anesthesia studies and can be stated succinctly. The induction of most forms of LTP requires activation of postsynapticN-methyl-D-aspartate (NMDA) receptors,163followed by influx of Na+ and Ca2+. This rise in intracellular Ca2+ is the critical trigger for LTP. Calcium-calmodulin-dependent kinase II (CaMKII) is then activated and autophosphorylated,164,165 leading to cytoskeletal reconfiguration.166 Activation of several other cell-signaling cascades also contribute to LTP. The terminal expression of LTP is protein synthesis, occurring in both the soma and local dendrites, and resulting in enduring structural changes at the synapse.167 Protein synthesis inhibitors have been demonstrated to consistently prevent sustained LTP in vitro and learning in vivo.168

Long-term Artificial Memory Processing

The overall AIS high-level memory architecture is shown in Figure 14.6. One thing to note is the connection between emotional memories and both explicit and implicit memories. Emotional memory carries both explicit and implicit characteristics.

Explicit or declarative memory is used to store conscious memories or conscious thoughts. Explicit memory carries information fragments that are used to create what most people would think of when they envision a memory. Explicit memory stores things such as objects and events, i.e., things that are experienced in the person’s environment. Information fragments stored in explicit memory are normally stored in association with other information fragments that relate in some fashion. The more meaningful the association, the stronger the memory and the easier it is to reconstruct or recall the memory when you choose to (Yang and Raine, 2009). In our AIS, explicit memory is divided into different regions, depending on the type or source of information. Regions are divided because different types of information fragments within the AIS memories are encoded and represented differently, each with their own characteristics, which makes it easier to construct or recall the memories, when the AIS later needs the memories. In the AIS LTM, we use fuzzy, self-organizing, contextual topical maps to associate currently processed information fragments from the STM with memories stored in the LTM (Crowder and Carbone, 2011a).

Long-term memory information fragments are not stored in databases or as files, but are encoded and stored as a triple helix of continuously recombinant binary neural fiber threads that represent:

The BIF object along with the BIF binary attribute objects

The BIF RNA binary relativity objects

The binary security encryption threads

Built into the RNA binary relativity objects are binary memory reconstruction objects, based on the type and source of BIF, that allow memories to be constructed for recall purposes.

There are several types of binary memory reconstruction objects:

Spectral eigenvectors that allow memory reconstruction using implicit and biographical LTM BIFs

Polynomial eigenvectors that allow memory reconstruction using episodic LTM BIFs

Socio-synthetic autonomic nervous system arousal state vectors that allow memory reconstruction using emotional LTM BIFs

Temporal confluence and spatial resonance coefficients that allow memory reconstruction using spatiotemporal episodic LTM BIFs

Knowledge relativity and contextual gravitation coefficients that allow memory reconstruction using semantic LTM BIFs

Memory

Memory is a term used to describe the cognitive mechanism by which information is acquired, retained, and recalled. Structurally, some major brain areas involved in memory processing include the hippocampus, fornix, temporal lobes, and cerebellum, with connections in and between most brain regions. The memory system can be partitioned into subsystems based on processing sequences; the form, time span, and method of recall; whether memories are conscious or unconsciously recalled; and the types of memory impairments that can occur.

Once information has been identified (through auditory, visual, tactile, and/or other sensory processes), it needs to beencoded and registered, a mental process that constructs a representation of the information into the memory system. The period (typically seconds) during which this information is being held and/or manipulated for registration, and ultimately encoded, consolidated, and retained, is referred to asworking memory. Other descriptors includeshort-term memory andimmediate memory.Consolidation andstorage represent the process by which information in short-term memory is transferred intolong-term memory. Information in long-term memory can be available for hours or as long as a life span. Long-term memories are generally thought to be housed, in whole or in part, in specific brain regions (e.g., cortex, cerebellum). Ordinarily, consolidation in long-term memory is accomplished in 1 or more of 4 ways: pairing 2 bits of information (e.g., a group of letters and the English sound it represents); storing procedures (consolidating new skills, e.g., the steps in solving mathematics problems); classifying data in categories (filing all insects together in memory); and linking new information to established rules, patterns, or systems of organization (rule-based learning).

Once information finds its way into long-term memory, it must be accessed. In general, information can be retrieved spontaneously (a process known asfree recall) or with the aid of cues (cued or recognition recall). Some other common descriptors of memory includeanterograde memory (capacity to learn from a single point in time forward),retrograde memory (capacity to recall information that was already learned), andexplicit memory (conscious awareness of recall),implicit memory (subconscious recall: no awareness that the memory system is being activated),procedural memory (memory for how to do things), andprospective memory orremembering to remember.Automatization reflects the ability to instantaneously access what has been learned in the past with no expenditure of effort. Successful students are able to automatically form letters, master mathematical facts, and decode words.

Long-Term Memory

Long-term memory in C. elegans has been demonstrated and extensively examined for mechanosensory learning (see Chapter 9). On the other hand, paradigms for long-term memory based on chemotaxis have only recently been developed in two laboratories. Both of these reports used odorants for chemotaxis and observed an association between butanone and food30 or 1-propanol and hydrochloride.31 In these assays, retention of the memory for approximately 1 day was demonstrated. Given many similarities between sensation of salt and odor, it is likely that a modified assay of salt chemotaxis learning will also lead to generation of a long-term memory.

Anterograde Amnesia—Inability to Create New Declarative Long-Term Memories After Hippocampal Lesions

The hippocampus is the most medial portion of the temporal lobe cortex, where it folds first medially underneath the brain and then upward into the lower, inside surface of the lateral ventricle. The two hippocampi have been removed for the treatment of epilepsy in a few patients. This procedure does not seriously affect the person’s memory for information stored in the brain before removal of the hippocampi. However, after removal, these people have virtually no capability thereafter for storingverbal and symbolic types of memories (declarative types of memory) in long-term memory or even in intermediate memory lasting longer than a few minutes. Therefore, these people are unable to create new long-term memories of those types of information that are the basis of intelligence. This condition is calledanterograde amnesia.

But why are the hippocampi so important in helping the brain to store new memories? The probable answer is that the hippocampi are among the most important output pathways from the “reward” and “punishment” areas of the limbic system, as explained inChapter 59. Sensory stimuli or thoughts that cause pain or aversion excite the limbicpunishment centers, and stimuli that cause pleasure, happiness, or sense of reward excite the limbicreward centers. All these together provide the background mood and motivations of the person. Among these motivations is the drive in the brain to remember those experiences and thoughts that are either pleasant or unpleasant. The hippocampi especially and to a lesser degree the dorsal medial nuclei of the thalamus, another limbic structure, have proved especially important in making the decision about which of our thoughts are important enough on a basis of reward or punishment to be worthy of memory.

4 Long-term Memory (LTM)

LTM is divided into two forms, an early LTM (eLTM, 1–3 days) characterized by protein synthesis-dependent PKC activity, but not by protein synthesis-dependent retention, and late LTM (lLTM, >3 days) protein synthesis-dependent retention and no enhanced PKC activity. The transition from lSTM to both forms of LTM appears to be independent of MTM, because inhibiting the characteristic substrate of MTM (protease-dependent enhancement of PKC activity) does not prevent eLTM and lLTM being formed (Fig. 1(B)). LTM requires multiple learning trials, indicating that specific information which can be extracted only from multiple experiences (signal reliability, context dependence) controls transfer to LTM. This transfer can be related to a change in the proportion of the activator and repressor forms of the PKA-responsive transcription factor CREB in Drosophila (Yin et al. 1995a, 1995b), but the role of CREB in the bee is still unknown. The picture emerging from findings on Drosophila is that LTM formation can be actively suppressed, rather than it being automatically produced with associative events accumulating and time elapsing. The balance between the activator and repressor form of CREB should therefore depend on the information content gained by multiple learning trials, rather than their mere accumulation, a proposal which needs to be tested.

Structural changes in the connectivity between neurons have been proposed as the substrates for LTM in vertebrates and invertebrates (Bailey et al. 1996) and are believed to be at least one target of the interference effects of protein synthesis inhibitors and memory blockers (for a review see Milner et al. 1998). In bees, direct evidence for LTM-related structural changes is lacking, but measurements of mushroom body subcompartment volume indicated that more experienced bees have bigger volumes and more elaborate dendrite branches (Durst et al. 1994, Fahrbach et al. 1995).

The biological circumstances of two forms of LTM may be related to the distinction between those forms of learning which usually lead to lifelong memories (e.g., visual and olfactory cues characterizing the home colony) and those which are stable but need updating on a regular basis (e.g., visual and olfactory cues of feeding places).

The bee, a small animal with a brain of merely 1 mm3 and a total of 950,000 neurons, establishes multiple and distributed memory traces not very different from mammalian memory in the general temporal dynamics, characteristics of contents, and cellular substrates. It may thus serve as a suitable model for the study of memory structure and formation.

Stages of Memory: Acquisition, Consolidation, and Retrieval

Long-term memory formation proceeds through three distinct phases: acquisition, consolidation, and retrieval (Abel and Lattal, 2001; McGaugh, 2000). Acquisition is the process of learning information about the world and initially produces a labile short-term memory that can be disrupted through interference by new learning, seizure, or inhibition of a variety of cellular and molecular processes. Consolidation occurs with time after learning to confer resistance to disruption, thus converting a short-term memory into a long-term memory. Once information has been stored, it must be retrieved to guide behavior. The specific processes that are required for the formation of long-term memory provide insight into the mechanisms responsible for each of these phases. For instance, disruptions that selectively affect long-term memory without impairing short-term memory provide knowledge about the consolidation process. The earliest of these studies showed that pharmacological inhibition of transcription or translation blocks long-term memory, while leaving short-term memory intact. In the 1960s and 1970s, researchers working on organisms ranging from goldfish to mice established that shortly after acquisition there are windows after learning during which transcription and translation are required to consolidate memory (Agranoff et al., 1967; Flexner et al., 1963; Squire and Barondes, 1970, 1976). These early pharmacological studies have been substantiated by genetic approaches that demonstrate a critical role of transcription factors in memory consolidation after learning.

Forgetting

Long-term memories are very enduring. Experimentally it is hard to distinguish between true forgetting and failure of retrieval, leaving open the possibility that long-term memory is actually permanent and any failures of recall are simply due to imperfect retrieval. Despite the difficulty in distinguishing true forgetting from failures of recall two main theories for how items may be forgotten from the long-term store have been developed. The first of these, decay theory, argues that memories decay over time. The second theory, interference theory, instead holds that the learning of related items leads to interference with subsequent forgetting of one or both items. There is, however, unfortunately relatively little experimental material that allows these theories to be clearly evaluated.

2.6 Long-term memories

Long-term memory stores are shown in the bottom row of boxes in Figure 2.10. These are the memory systems for autobiographical episodes, for various kinds of knowledge, and for highly practiced expertise. Once these memories are stored, they are not conscious. However, they can be retrieved from memory and again enter into the memory (Figure 2.11).

Long-term memory traces are located in many places, as we will see. These may include the entire cortex and subcortical structures like the basal ganglia and cerebellum. But almost everything we can see in Figure 2.1 is the more recent cortex, called the neocortex (the more recent mammalian cortex, as opposed to the ancient cortex of reptiles and earlier vertebrates). Neocortex has expanded greatly over mammalian evolution, accelerating during primate and hominin evolution over the last 4 million years.

6.4 Learning, recall, and long-term memory

Long-term memories require learning and repetition to become fixed, and once stored they can last a long time and be retrieved by triggers or cues. For example, seeing a specific door handle triggers a memory that the door should be pulled to open rather than pushed, without needing to read the sign on the door.

Prior use of a product enables us to learn aspects of its features and use that are held in long-term memory, and make it easier to use in the future. To maximize learning the product must provide good feedback so that the users can immediately see the result of their actions and adjust them if necessary. The brain can learn to associate symbols, shapes and colors with particular features or functions, provided sufficient support is available by explanatory text and visual layout. For example, learning the symbols for the buttons used on the toolbar of a word editor is dramatically enhanced if explanatory text appears when the mouse is left over the symbol.

Long-term memory may be transferred to help learn and understand other similar products. Our ability to learn decreases with age, and older generations that did not grow up with technology products lack the prior experience to understand functions that the designer may have considered obvious, which is why user testing is crucial to ensure usability.