Memory consolidation
Memory consolidation is a category of processes that stabilize a memory trace after its initial acquisition. A memory trace is a change in the nervous system caused by memorizing something. Consolidation is distinguished into two specific processes. The first, synaptic consolidation, which is thought to correspond to late-phase long-term potentiation, occurs on a small scale in the synaptic connections and neural circuits within the first few hours after learning. The second process is systems consolidation, occurring on a much larger scale in the brain, rendering hippocampus-dependent memories independent of the hippocampus over a period of weeks to years. This involves several mechanisms including molecular, synaptic, and systems-level processes that stabilize newly formed memories. Recently, a third process has become the focus of research, reconsolidation, in which previously consolidated memories can be made labile again through reactivation of the memory trace.
History
Memory consolidation was first referred to in the writings of the renowned Roman teacher of rhetoric Quintillian. He noted the "curious fact... that the interval of a single night will greatly increase the strength of the memory," and presented the possibility that "... the power of recollection.. undergoes a process of ripening and maturing during the time which intervenes." The process of consolidation was later proposed based on clinical data illustrated in 1882 by Ribot's Law of Regression, "progressive destruction advances progressively from the unstable to the stable". This idea was elaborated on by William H. Burnham a few years later in a paper on amnesia integrating findings from experimental psychology and neurology. Coining of the term "consolidation" is credited to the German researchers Müller and Alfons Pilzecker who rediscovered the concept that memory takes time to fixate or undergo "Konsolidierung" in their studies conducted between 1892 and 1900. The two proposed the perseveration-consolidation hypothesis after they found that new information learned could disrupt information previously learnt if not enough time had passed to allow the old information to be consolidated. This led to the suggestion that new memories are fragile in nature but as time passes they become solidified.Systematic studies of anterograde amnesia started to emerge in the 1960s and 1970s. The case of Henry Molaison, formerly known as patient H.M., became a landmark in studies of memory as it relates to amnesia and the removal of the hippocampal zone and sparked massive interest in the study of brain lesions and their effect on memory. After Molaison underwent a bilateral medial temporal lobe resection to alleviate epileptic symptoms the patient began to suffer from memory impairments. Molaison lost the ability to encode and consolidate newly learned information leading researchers to conclude the medial temporal lobe was an important structure involved in this process. Molaison also showed signs of retrograde amnesia spanning a period of about three years prior to the surgery suggesting that recently acquired memories of as long as a couple years could remain in the MTL prior to consolidation into other brain areas. Research into other patients with resections of the MTL have shown a positive relationship between the degree of memory impairment and the extent of MTL removal which points to a temporal gradient in the consolidating nature of the MTL.
These studies were accompanied by the creation of animal models of human amnesia in an effort to identify brain substrates critical for slow consolidation. Meanwhile, neuropharmacological studies of selected brain areas began to shed light on the molecules possibly responsible for fast consolidation. In recent decades, advancements in cellular preparations, molecular biology, and neurogenetics have revolutionized the study of consolidation. Providing additional support is the study of functional brain activity in humans which has revealed that the activity of brain regions changes over time after a new memory is acquired. This change can occur as quickly as a couple hours after the memory has been encoded suggesting that there is a temporal dimension to the reorganization of the memory as it is represented in the brain.
Synaptic consolidation
is one form of memory consolidation seen across all species and long-term memory tasks. Long-term memory, when discussed in the context of synaptic consolidation, is conventionally said to be memory that lasts for at least 24 hours. Synaptic consolidation is achieved faster than systems consolidation. There is evidence to suggest that synaptic consolidation takes place within minutes to hours of memory encoding or learning, and as such it is considered the 'fast' type of consolidation. It is also referred to as 'initial consolidation'. As soon as six hours after training, memories become impervious to interferences that disrupt synaptic consolidation and the formation of long-term memory. Late-phase LTP, the long-lasting form of one of the best understood forms of synaptic plasticity, is thought to be the cellular process underlying synaptic consolidation.Standard model
The standard model of synaptic consolidation suggests that alterations of synaptic protein synthesis and resulting changes in membrane potential are achieved through activating intracellular transduction cascades. These molecular cascades trigger transcription factors that lead to changes in gene expression. The result of the gene expression is the lasting alteration of synaptic proteins, as well as synaptic remodeling and growth. In a short time-frame immediately following learning, the molecular cascade, expression and process of both transcription factors and immediate early genes, are susceptible to disruptions. Disruptions caused by specific drugs, antibodies and gross physical trauma can block the effects of synaptic consolidation.Synaptic Plasticity
Additionally, synaptic consolidation is supported by multiple forms of synaptic plasticity. Synaptic plasticity is largely defined as the ability of a neural connection to change in strength over time due to exposure to different levels of stimuli. In other words, an organism's neural connections can adapt and change to accommodate different environmental stimuli which can have larger systemic effects. Some mechanistic examples of this include long-term potentiation and long-term depression. Long-term potentiation is an increase in the strength of a synaptic input as a result of repeated high-frequency stimulation. In other words, neural responses across two neurons strengthen over time the more those neurons fire. In contrast to long-term potentiation is long-term depression, which results from low-frequency or lack of stimulation. In conjunction, this means that synaptic connections between neurons can either increase or decrease in strength due to frequency or intensity of use. Global implications of this can be found in brain areas such as the hippocampus, where one study on rabbits demonstrated that repeated stimulation of hippocampal neurons led to an increase in the future efficacy of their activation.Long-term potentiation
LTP can be thought of as the prolonged strengthening of synaptic transmission, and is known to produce increases in the neurotransmitter production and receptor sensitivity, lasting minutes to even days. The process of LTP is regarded as a contributing factor to synaptic plasticity and in the growth of synaptic strength, which are suggested to underlie memory formation. LTP is also considered to be an important mechanism in terms of maintaining memories within brain regions, and therefore is thought to be involved in learning. There is compelling evidence that LTP is critical for Pavlovian fear conditioning in rats suggesting that it mediates learning and memory in mammals. Specifically, NMDA-receptor antagonists appear to block the induction of both LTP and fear conditioning and that fear conditioning increases amygdaloidal synaptic transmission that would result in LTP.Structural Plasticity
In order to discuss how memory consolidation works on a broader scale we have to also acknowledge the broader mechanisms of plasticity that occur outside of the synapse. This brings us to the process of structural plasticity. Structural plasticity represents changes in the broader cell, encompassing both changes in neuron shape, changes in supporting cell shape, and formation of new cells entirely. Because memory consolidation involves the long-term stabilization of neural circuits, these large-scale structural changes are thought to contribute to the persistence and organization of consolidated memories. The following is a brief list of some of the most significant mechanisms of plasticity in the brain.Neurogenesis
which is the brains process of making new neurons. While this has not been demonstrable in adult humans, neurogenesis is a major contributor to brain plasticity in other organisms such as rodents. However, it has been proposed that newly generated neurons in the hippocampus can integrate into memory-related circuits in newborns, and this process has been proposed to support certain forms of memory consolidation—particularly those involving pattern separation or long-term retention.Synaptic Remodelling
However, this is not the only possible mechanism that enables structural changes in neurons. Dendritic spine remodelling is one of the primary mechanisms by which neuroplasticity is derived. Dendritic spines are signal receiving locations on neurons found on dendrites. There are many types of spines that possess different functions, however the important aspect of them is that their shape and frequency is flexible. Furthermore, there seems to be a direct connection between changes in spines and experiences in rodents, and dendritic spine remodelling has been established as a significant component in learning and memory. Because memory consolidation requires the stabilization of experience-dependent synaptic changes, long-term alterations in spine number, size, or morphology are thought to provide a structural substrate for the maintenance of consolidated memories. This is important as it indicates a direct relationship between experiences and neurological changes. Additionally, spine concentration on a neuron is subject to fluctuation, with that fluctuation relating to regularity of activation. Studies suggest that increased activation of neurons can lead to increases in formation of spines, while over activation can cause loss of them. This fluidity in spine density provides a further mechanism for neurons to adapt in sensitivity. In summary, due to the combined characteristics of high flexibility of structure and function, as well as the ability to fluctuate in concentration, dendritic spines, via dendritic spine remodelling provides an immense amount of flexibility in the brain. These spine-level changes are believed to play a key role in converting transient synaptic modifications into long-lasting memory traces.In addition to the aforementioned processes are synaptogenesis and synaptic pruning. Synaptogenesis is the process by which a two neurons form a new synapse, and synaptic pruning is the process by which a synaptic connection between two neurons is eliminated. In short, these two mechanisms allow for changes in neural connections, facilitating processes of connection formation and connection degradation. This allows for a high level of variability in neural pathways as they can be subject to change based on different conditions. By acting as a mechanism that mediates overall synaptic changes, synaptogenesis and pruning can modify how information is routed and stored over time, thereby influencing the long-term consolidation of memories.