Abstract: Hippocampus is considered as the key structure of memory acquisition, initial storage and retrieval. This paper discusses how the memory originally dependent on hippocampus is finally expressed in the cortex, and how the memory changes with time. The conclusion of this paper is that TTT theory provides a new way to think about reorganization and consolidation. As a continuous interactive process, it is related to hippocampus, medial prefrontal cortex mPFC and other brain regions.
introduce
There are two schools of argument about memory reorganization. One group thinks that the memory trace is fixed in the original form, while the other group thinks that this process is constantly developing. After the memory and reactivation, the memory will be updated to the new version. There are generally two ways to explain the process of memory consolidation: cell (or synapse) consolidation and system consolidation. This paper traces the interaction between hippocampus and cortex in TTT theory, and considers the similarity between the memory consolidation mechanism of rodents and human memory.
How are memory traces formed? Mechanism of cell integration
When an experienced event turns into long-term memory, it is necessary to form memory traces in the brain and exist in a group of neurons in the form of synaptic connections. During this period, it needs to induce neuronal depolarization and intracellular calcium influx, leading to the transcription and translation of plasticity-related protein PRPs. PRPs induces changes in the structure and function of local neural networks, leading to new, remodeled or enhanced synaptic connections. These changes took place within a few minutes to a few hours after the incident, and it took a period of calm to stabilize. Protein's inhibition of synthesis or the interference of new learning time will interrupt this process, destroy the stable process and lead to incomplete consolidation.
A special transcription factor CREB is considered as an important memory gene. Similar effects have been found in rodents.
Evidence: 1. Regulation is involved in the expression of many PRPs, including growth factors, structural proteins, signal transduction proteins and so on.
2.？ CREB-mediated transcription leads to the enhancement of excitability and plasticity of neurons, and activates the structural changes of cell neuron morphology.
3.？ Even if the learning environment is weak, it can promote memory consolidation.
4.？ It can be considered that increasing CERB level promotes the consolidation of weak coding memory.
In the memory allocation paradigm, continuously presented items will be coded by overlapping neuron groups, so after an item is put forward, the same group of neurons connected with it may be activated, so that items will be related in the retrieval process, and those that are close in time are often combined in the retrieval.
Protein synthesis dependence observed in rodents may be the basis of human memory consolidation, but it has many limitations in human research, and cell consolidation has no good characteristics in humans. Moreover, when human beings study multiple projects, each project goes through its own merging process, and subsequent projects will become interference, making it difficult to integrate information. Although it is impossible to form a firm and lasting memory in a completely undisturbed environment, it is not clear how to do this. There is a hypothesis that the hippocampus supports the unique expression of different memories and is relatively resistant to the interference of subsequent projects. In the cortex, familiar memories that are not affected by this mechanism of hippocampus will be more easily disturbed.
How do memory traces change with time? Reorganization and distribution of memory networks
After the window period of cell consolidation is over, the memory trace will be stabilized and will not be interfered by protein's synthetic inhibition, pharmacological destruction and new learning. Memory traces will be transformed into a longer system consolidation process, forming new synaptic connections in the neural network of the whole brain.
Both hippocampus and cortex will form traces when memory is acquired, but the traces of cortex will be consolidated over time. It is not clear whether the hippocampus also plays a lasting role in memory storage and retrieval.
SCT Standard Integration Theory Standard Consolidation Theory: Hippocampus plays a limited role in the storage of declarative memory. With the passage of time, memory forms new memory traces in the cortex, and with the enhancement of surface memory traces, the traces in the hippocampus will weaken until they leave the hippocampus. Evidence: It is not necessary to store and extract semantic memory in the hippocampus of MTL patients and TGRA patients with retrograde amnesia. These patients forget the situational memory, but the semantic memory will remain. This separation cannot be explained by SCT.
MTT multiple trace theory multiple trace theory: Memory traces in the cerebral cortex are some * * * identical elements, which will be repeatedly activated over time and then integrated into the existing knowledge network. Memory reactivation can also form a variety of memory traces with different distributions, and the hippocampus stores situational memories and more detailed memories.
Trace transformation theory: A complete brain has two versions of memory, one depends on the hippocampus version in detail, and the other is the generalized semantic cortex version. The extraction conditions affect the expression of which version of memory. If you don't need specific details, you will only activate cortical memory. If you need details or scenes, you will search the hippocampus version, but the cortex may still be involved. TTT predicts that as long as the retrieved memories retain the perceptual details, the hippocampus will have similar activities, whether it is distant memories or recent memories. Specific situational memory and transformed generalized memory will exist.
Studies on rodents show that the aCC region in mPFC is a region involved in remote memory, and both aCC and hippocampus can independently indicate the expression of memory, in other words, inactivating one of them alone will not affect retrieval. The damage of mPFC will affect human situational memory, but there is no evidence that it is related to remote memory. People's destruction of mPFC will also cause serious memory distortion, and subjects will also take leave. The mechanism of the defect behind this memory distortion is still under debate, which will lead to the inability to retrieve the desired target correctly and damage the individual's ability to suppress irrelevant memory.
MPFC combines the research of humans and rodents, participates in the processing and expression of schema schemes, guides the coding and extraction of perception and memory, provides template comparison and retrieval of memory, thus ensuring the final expression of correct information. In humans, this mechanism will damage mPFC in the form of memory distortion, and rodents will show memory loss due to lack of oral reports. It can be speculated that when memory depends on schema, it will be damaged, but if it is very clear, the memory guided by clues will not be damaged.
A case of spatial memory transformation
It has always been thought that spatial memory depends on the cognitive map of hippocampus. Later, it was found that memories acquired more than a year ago that have become familiar with the environment will not activate the hippocampus, but recent memories will activate the hippocampus. This ability to reserve space depends on a schematic terrain representation, which can be supported by the external expression of hippocampus, but the specific and rich environment still needs the internal expression of hippocampus.
For example (Winocur G, Moscovitch M, Fogel S, Rosenbaum RS, Sekeres M (2005b)) Spatial Memory after Hippocampus Attack: The Influence of Extensive Experience in Complex Environment. NAT Neurosci 8: 273–275) Rats were placed in a "village" for several months, and then the hippocampus was damaged. There is no problem with the original environment and familiar route memory, but after resetting the environment, there is obvious spatial memory disorder.
For example, Ciaramelli E (2008) The role of exotic prefrontal cortex in navigation: a case of imported pathfinding and rehabilitation. Neuropsycholia 46 (7): 2099–2105 Participants (patients with ventral medial prefrontal lobe injury) were asked to travel from a familiar place to another place, and sometimes they got lost. This defect seems to be due to the inability to exclude distracting or disturbing spatial information, such as following an inappropriate route triggered by clues in the environment when navigating to a specified location, rather than losing the spatial information of distance learning.
Evidence of System Integration and Memory Transformation in Healthy Rodents' Brain
Hippocampus and structures outside hippocampus interact in memory retention and retrieval. Some traces of original memory are preserved by hippocampus, which is helpful for remote memory extraction. When the hippocampus is damaged, the kinetic energy of the whole network will be destroyed, but other networks can gradually adapt to and make up for the hippocampus damage. When the original memory is inaccessible, other components of the memory network can support retrieval, but the retrieved memory is generalized and lacks scenes and details.
Evidence: Goshen I, Brodsky M, Prakash R, Wallace J, Gradi Naru V, Ramakrishnan C,
Dynamics of Deisseroth K (20 1 1) remote memory retrieval strategy. Cell147: 678–689 Using the fast optogenetics method, by detecting the contribution of hippocampal CA 1 neurons, even after a few weeks, the photoinhibition of CA 1 neurons can eliminate fear memory (remote memory). The extraction of long-term memory usually depends on the hippocampus, but it can still be transferred to alternate structures.
Limitations of memory consolidation model in rodents
Up to now, there is no remote memory network in the whole brain region of rodents (because of the huge workload). In the existing research, hippocampus is a key hub connecting several regions, but how the damage of this node changes the activity and functional connection needs further study.
Evidence of System Integration and Memory Transformation in Healthy Human Brain
In healthy individuals, after 1 week, with the disappearance of situational memory, hippocampal activity decreases, but the remote autobiographical situational memory with vivid and perceptual details is still related to high hippocampal activity. Remote autobiographical memory is also related to PFC.
For example, Sekeres MJ, Bonasia K, St-Laurent M, Pishdadian S S, Winocur G, Grady C, Moscovitch M (20 16a) verify and prevent the loss of detail memory: the difference of forgetting rate of detail types in situational memory. Learning Memory 23: 72–82 uses the memory of movie clips to determine how different elements of situational memory change over time. Consistent with TTT's prediction, the following points were found: (1) After coding, the perceptual details were extracted immediately, and the hippocampus was active; (2) With the passage of time, the memory of perceptual details decreases, while the central story elements remain. Seven days ago, the activity of hippocampus decreased and the activity of mPFC increased. (3) Whether the vivid detailed memory is extracted immediately or after 7 days, the hippocampus is active, and the cortex has strong activity support after 7 days (this is consistent with TTT prediction).
The detailed version of memory and the semantic graphic version related to it can be saved, interacted, compensated, accessed by different clues and activated under different task conditions.
What is the mechanism of system integration?
Another possible mechanism related to remodeling is reconsolidation. When the memory is activated, the memory trace will be in a temporarily unstable state, which is easy to be destroyed and changed. If it is to be preserved, it needs further reinforcement.
Research on rodents found that:
(1) Long-distance memory experienced a reconsolidation process similar to protein's synthetic dependence system in hippocampus.
(2) Viral increase of PKMf can enhance the retrieval of consolidated memory, and enhancing cortical plasticity may promote the consolidation of the system.
Research on the consolidation of human memory;
(1) "Active consolidation in sleep", offline hippocampus offline-hippocampus can be activated and replayed during slow-wave sleep or rest, so that memory traces are distributed to the cortex. Synaptic consolidation wave (promoting the changes of synaptic strength and nerve transmission efficiency of cortical neural network) can be regarded as a subroutine of memory consolidation. Some memories that are rarely activated experience fewer synaptic consolidation waves, so they will not form multi-distribution traces.
(2) The reactivation and subsequent consolidation of memory will lead to the change of existing memory traces, rather than the elimination.
For example, St. Jacques PL and Schacter DL (20 13) modify memory to selectively enhance and update the personal memory of museum visits by responding to personal memory. Psychological Science 24: 537–543 Participants visited the museum with their cameras. Presenting photos taken by yourself and photos taken by other routes in the museum in the test will better activate the memory of photos with high matching, but at the same time, reactivation will also increase the false memory of new photos.
The wrong recognition of photos is related to hippocampus and vmPFC, and it is also considered to be related to memory conversion in TTT theory.
Timetable for system integration
With the passage of time, the specific scale and time of memory network reorganization and distribution are still uncertain. Previous studies have obtained the following information: (1) The large-scale reorganization of declarative memory network is within 24 hours of associative memory acquisition and within one week of film editing complex plot memory coding; (2) The reorganization of autobiographical memory can last for several months to several years (the reorganization of memory network may last for a lifetime); (3) The episodic memory of rodents can activate hippocampal neurons for two days, but it is less activated after two weeks, and the memory may be transformed into mPFC traces.
The formation of remote memory is related to the growth of dendritic spines in aCC. Spine aggregation can promote the development of situational memory after imprinting, such as Govindarajan A, Kelleher RJ, Tonegawa S (2006), a clustering plasticity model of long-term memory imprinting. Journal of Neuroscience 7: 575–583. Cortical plasticity may be related to consolidating the interaction between cortex and hippocampus in the early stage.
For example, Vetere G, Restivo L, Cole CJ, Ross PJ, Ammassari-Teule M, Josselyn SA, Frankland PW (20 1 1) spinal growth in the antenna cortex is necessary for the consolidation of situational fear memory. Procnatl acadsci108: 8456–8460 The consolidation of situational fear memory in rats is related to the dendritic growth of aCC neurons. When MEF2 is used to inhibit synaptic growth, it is found that it will hinder the growth of consolidation-related dendritic spines and the subsequent memory expression during the training window.
Conclusion: Change the concept of merger.
Consolidation means continuous transformation, not simple fixation, which is a dynamic and nonlinear process. TTT theory holds that hippocampus and mPFC are a continuous interactive process, which provides a new direction for the structure of brain memory network.