Nature: Does pressing the synaptic ON/OFF key really switch memory mode?

Click on the blue word to focus on our drug addiction will cause nonadaptive reward memory related to drug cues, thus promoting subsequent drug seeking and relapse.this kind of memory is similar to other forms of memory. Previously formed and consolidated drug memory can be recovered when it is exposed to drug-related clues again. In the process of recovery, drug-related memory is temporarily unstable and becomes easy to be destroyed, but this memory will be consolidated again to form a stable memory.the brain response to addictive drugs is mainly manifested in the adaptive changes of neurons and synaptic plasticity changes. The former can explain the important characteristics of addiction, and the latter is the basis of memory and can explain the continuous relapse behavior.NAC, prefrontal cortex, hippocampus, VTA and other brain regions are the main brain regions in the process of addiction.silent synapse refers to synapses with synaptic structure but no transmission function under physiological conditions, that is to say, it contains NMDA receptor, but there is no stable AMPA receptor.when an individual takes cocaine, silent synapses are produced. Only a part of silent synapses form functional synapses through the recruitment of AMPA receptors after cocaine relapse.December 2, 2019, Yan Dong research team, Department of neuroscience, University of Pittsburgh, published silent synapses dictate cocaine memory degradation and reconsolidation in the journal Nature Neuroscience, revealing the important role of silent synapses in the stabilization and reconsolidation of cocaine memory.the researchers trained the rats to match the light and cocaine. After 5 days of continuous training, the rats successfully acquired the clue related cocaine memory, which showed that the behavior of seeking cocaine increased, and it was more obvious after 45 days of relapse.further electrophysiological analysis showed that the number of silent synapses in NAC increased on the first day of relapse, but decreased on the 45th day.this is consistent with previous studies that silent synapses may recruit AMPA receptors to form mature synapses during memory consolidation.in this process, what is the effect of light on the retrieval and de stabilization of cocaine memory? The number of silent synapses in NAC did not increase after exposure to light.however, the percentage of silent synapses exposed to light was increased in cocaine trained rats exposed to light again compared with cocaine rats without light pairing training.the percentage of silent synapses remained high after 2 or 4 hours of light exposure, but returned to a low level after 6 hours (memory reconsolidation stage was entered after 6 hours).after 6 hours of administration of AMPA receptor inhibitors, memory was destroyed and reconsolidated, and the proportion of silent synapses was increased again.this indicates that the silent synapses induced by light rays are recruiting AMPA receptors to form mature synapses.these data indicate that memory retrieval can destroy the stability of cocaine memory and form silent synapses again, and these silent synapses will mature in the subsequent memory reconsolidation period.the morphological changes of dendritic spines are highly related to the formation of synapses. at present, it is generally believed that the mushroom type dendritic spines represent mature synapses rich in AMPA receptors, while the elongated and filiform pseudopodiform dendritic spines almost have no AMPA receptors, so they represent immature synapses. morphological experiments showed that cocaine could increase the total density of dendritic spines in NAC on the first day after training and relapse, which was mainly contributed by slender dendritic spines. on the 45th day after relapse, the total density of dendritic spines in this brain region was still increased, but the proportion of slender dendritic spines decreased to normal level, while mushroom type dendritic spines increased. to some extent, this indicates that synaptic maturation is promoted in the memory consolidation stage. surprisingly, re exposure to light after 45 days did not change the density of dendritic spines, but the density of mushroom type dendritic spines decreased to normal level, and the density of slender dendritic spines increased, which recovered after 6 hours of exposure. this further indicates that re exposure leads to the instability of mature synapses and the formation of immature synapses. At the end of the destabilization window, these immature synapses become mature again, which is consistent with the previous electrophysiological experimental data. so what is the molecular mechanism of cocaine memory instability mediated by silent synapses? The researchers focused on Racl, a GTPase that belongs to the Ras superfamily of small GTP binding proteins. Racl protein regulates actin cytoskeleton through limk cofilin signaling pathway to maintain synaptic stability. enzyme linked immunosorbent assay (ELISA) was used to observe that Racl activity in NAC brain region of rats decreased briefly after 45 days of re exposure to light, and returned to normal level after 6 hours. the Rac1 knockdown activity was further achieved by constructing HSV virus, which did not affect the silent synapses at normal levels. therefore, the researchers injected HSV into NAC brain area after 45 days of relapse can increase the proportion of silent synapses (since the virus can be highly expressed after 12-16 hours, this time window belongs to memory reconsolidation period), making memory unstable again. photogenetic inhibition of Rac1 activity in this brain region produced similar results. the same HSV was constructed to activate Rac1 activity. The Rac1 activity was activated by light 12 hours after the virus was injected into NAC brain area. At this time, the proportion of silent synapses in NAC brain area did not increase, indicating that even external intervention could not destroy the stability of memory after increasing Rac1 activity. this suggests that Rac1 plays a key role in the transition between silent and mature synapses. in conclusion, cocaine training can promote the formation of silent synapses, which become mature synapses through the recruitment of AMPA receptors during subsequent memory consolidation. during the process of memory retrieval, the stability of memory will be destroyed and the mature synapses will become immature again. Rac1 protein plays a central role in this random switching mode between silent and mature synapses. references; William J. Wright, Nicholas M. Graziane， Peter A. Neumann；Silent synapses dictate cocaine memory destabilization and More terrible than soreness is that lactic acid accumulation destroys hippocampal nerve regeneration. Cell sub Journal: oligodendrocytes reappear new functions - maintain memory consolidation Science: may subvert cognition - aging gut The communication group 1 autism communication group 2 depression communication group 3 animal model communication group 4 PD communication group 5 neuroscience clinician communication group 7 literature sharing discussion exchange group 8 ad communication group 9 anxiety group 10 group learning and memory exchange group, WeChat public response number 1, pull 1 in the field of neuroscience, everyone concerned about the official account, attention to official account reassignment, contribution, cooperation and other related matters. Please add WeChat: long, according to two-dimensional code attention, we listen to people who have seen will click on "see".