Memory consolidation

Memory consolidation is a category of processes that stabilize a memory trace after its initial acquisition. Consolidation is distinguished into two specific processes, synaptic consolidation, which is synonymous with late-phase long-term potentiation and occurs within the first few hours after learning, and systems consolidation, where hippocampus-dependent memories become independent of the hippocampus over a period of weeks to years. 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. Memory consolidation is a category of processes that stabilize a memory trace after its initial acquisition. Consolidation is distinguished into two specific processes, synaptic consolidation, which is synonymous with late-phase long-term potentiation and occurs within the first few hours after learning, and systems consolidation, where hippocampus-dependent memories become independent of the hippocampus over a period of weeks to years. 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. 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 (MTL) was an important structure involved in this process. Molaison also showed signs of retrograde amnesia spanning a period of about 3 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, or late-phase LTP, 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 memory that lasts for at least 24 hours. An exception to this 24-hour rule is long-term potentiation, or LTP, a model of synaptic plasticity related to learning, in which an hour is thought to be sufficient. Synaptic consolidation is achieved faster than systems consolidation, within only minutes to hours of learning in goldfish. LTP, one of the best understood forms of synaptic plasticity, is thought to be a possible underlying process in synaptic consolidation. The standard model of synaptic consolidation suggests that alterations of synaptic protein synthesis and 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. 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. Synaptic consolidation, when compared to systems consolidation (which is said to take weeks to months to years to be accomplished), is considerably faster. There is evidence to suggest that synaptic consolidation takes place within minutes to hours of memory encoding or learning, and as such is considered the 'fast' type of consolidation. As soon as six hours after training, memories become impervious to interferences that disrupt synaptic consolidation and the formation of long-term memory. Distributed learning has been found to enhance memory consolidation, specifically for relational memory. Experimental results suggest that distributing learning over the course of 24 hours decreases the rate of forgetting compared to massed learning, and enhances relational memory consolidation. When interpreted in the context of synaptic consolidation, mechanisms of synaptic strengthening may depend on the spacing of memory reactivation to allow sufficient time for protein synthesis to occur, and thereby strengthen long-term memory.