Cell: The evidence is conclusive! Memory trace cell groups are also subtyped.

Learn about the latest advances in neuroscience ● click the blue word to focus on us ● each memory imprint contains a sparse group of neurons that are activated after a specific learning experience and undergo long-term synaptic modification (1).in fact, there has always been a problem: since memory can be expressed in different forms or modified in many ways, then in a specific memory imprint, the function of these neurons is the same or different (2,3).in fact, some researchers prefer that the functions of neurons in memory imprinting are different. Theoretically, different types of neuronal activation are more conducive to encoding information, so that they can flexibly express memory in a rapidly changing environment.in the process of learning and memory, many types of neurons can be activated.that is, the early gene (IEG) gene coding activity reporter genes Fos and arc are mainly used to identify the neurons activated under specific behaviors or activities.at present, most of the imprinted cells use an early gene reporter mouse as a research tool, so they can recognize a type of neuronal population.FOS mainly regulates the long-term potentiation of excitatory synapses, while npas4 mainly recruits inhibitory synapses to excitatory neurons (4), which can also be used as IEG.based on Fos and npas4, the synaptic functions are different, and the neuron groups defined by them are also different in function.on April 16, 2020, Dr. Yingxi Lin of Massachusetts Institute of Technology (MIT) published an article in the journal Cell, which combined Fos and npas4 to label different cell types in the same imprinted cell group, revealing the heterogeneity of imprinted cells and further discovering their roles in memory differentiation and memory generalization balance.researchers have constructed a Fos and npas4 activity marker (RAM) reporting system, which is f-ram and n-ram respectively, which can specifically label the active neuron population dependent on Fos and npas4.further, after fear memory training, the microexcitatory postsynaptic current of f-ram labeled neurons increased, while that of n-ram labeled neurons increased, which is consistent with the previous research results. However, the heterogeneity of synaptic function may lead to differences in memory expression.then where does the excitatory input of f-ram labeled neurons in DG brain come from? Where do n-ram labeled neurons receive inhibitory inputs? Previous studies have shown that the entorhinal cortex projects to DG through the medial perforator pathway (MPP) and the lateral entorhinal cortex projects through the lateral perforating pathway (LPP). The mossy cell fibers derived from dentate hilus can also reach DG (5).after fear memory training, the f-ram labeled neurons in the entorhinal cortex DG pathway were specifically enhanced, and the inhibitory inputs recruited near nram labeled neurons mainly came from cholecystokinin inhibitory neurons (CCK +) in DG area. Experimental plan, picture from 7 After 24 hours, the mice were put back into environment a, B or C (the exposure of the original environment or new environment is called memory retrieval). Finally, it was found that the rate of fear rigidity of mice re placed in environment a was the highest, that of environment B was higher than that of environment C.the proportion of f-ram labeled neurons is similar in environment a and B, but smaller in environment c, which indicates that f-ram labeled neurons are not sensitive to similar environmental changes and are more conducive to memory generalization; on the contrary, the proportion of n-ram labeled neurons in environment a is significantly less than that in environment B, and the proportion in environment c is also less, which means that n-ram labeled neurons are not coding Memory of the new environment, but can distinguish the difference between environment a and environment B, these two types of cells are not very sensitive to the new environment.this result was verified in the experiment of fiber optic calcium imaging recording system.for a long time, "memory coding accuracy theory" has been the mainstream in memory theory. The theory holds that when memory retrieval and memory coding are in the same environment, the highest efficiency of "memory precision retrieval" (6) will appear.however, it is very unlikely that this kind of condition is exactly the same, as Heraclitus famously said: it is impossible for a person to step into the same river twice. In most cases, the generalization mechanism of memory retrieval is more in line with the real world.simply speaking, fear generalization means that fear will occur in a similar environment after receiving stimulation in a certain environment.memory generalization is also considered to be a flexible and adaptive behavior in the face of changing environmental stimuli, and can quickly respond to danger.of course, excessive memory generalization can cause anxiety and post-traumatic stress disorder.in the face of danger, it is also important to distinguish between threat and non threat (Security) signals.in this paper, environment B is a similar environment compared with environment A. although there are great similarities between them, there are some differences.similar parts produce memory generalization process, while different parts produce memory differentiation process.the effect of chronic inhibition of f-ram labeled neurons or activation of n-ram labeled neurons by chemical genetics technology is consistent, which can enhance the differentiation ability of mice to environment a and environment B. activation of f-ram labeled neurons or inhibition of n-ram labeled neurons can weaken the differentiation ability of mice to environment a and environment B. these operations have no effect The ability of mice to distinguish environment a and environment C.these results can explain two problems: first, f-ram labeled neurons encode information of the same memory expressed in almost the same environment, which is a kind of memory generalization; while n-ram labeled neurons encode the information of the same memory which is different but similar to the environment, which is a process of memory differentiation.Second, there is a balance between memory generalization and memory differentiation, which can be changed by regulating the above two types of neurons.Third, the ability of f-ram labeled neurons and n-ram labeled neurons to express memory in the new environment is very weak.after chronic inhibition of neuronal activity in the entorhinal cortex, the ability of mice to distinguish between environment a and environment B was also enhanced. Photogenetics inhibited the DG neural circuit of entorhinal cortex and showed similar results. However, chronic inhibition of CCK positive neurons in the DG area weakened the ability of mice to distinguish between environment a and environment B, which indicated that entorhinal cortex DG had a similar effect The neural circuits control the process of memory generalization, while CCK positive neurons in DG area control the process of memory differentiation.in general, by developing Fos and npas4 activity marker (RAM) reporting system, we have labeled different types of neurons in the imprinted cells of DG brain region under fear training, and further confirmed that the function of neurons in memory imprinting is different, F-ram labeled neurons encode the generalization of relevant information, while n-ram labeled neurons encode and distinguish relevant information. 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