High-yield team—Professor Gao Tianming once again reveals the molecular mechanism that regulates the disappearance of fearful memories

Click the blue word to pay attention to our serious traumatic events will produce persistent, negative memories in the brain, which may later develop called post-traumatic stress disorder (PTSD)
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The dissipation of fear memory is the main process of overcoming conditioned fear
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The formation of this dissipated memory is unstable at first and eventually forms a stable memory
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This process of memory consolidation relies on changes in synaptic plasticity on a time scale of minutes to hours or the integration of neural circuits on a time scale of weeks to years
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The medial prefrontal cortex is the core brain area that regulates fear memory, and can be further subdivided into the subliminal cortex (IL) and the anterior marginal cortex (PL)
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Paralbumin (PV) positive inhibitory mesenteric neurons are the main neuron type in the cortex.
They inhibit the cell body and proximal dendrites of neurons forming around the cell body, and play a key role in the formation of neural oscillations
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Studies have shown that experience or environment-dependent memory changes are achieved by targeting PV neurons in different stages of differentiation
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PV neurons that express low levels of paralbumin and GAD67 and receive high-density inhibitory synaptic input are called poorly differentiated PV neurons; express high levels of paralbumin and GAD67 and receive high-density excitatory synapses The input PV neurons are called well-differentiated PV neurons
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On October 25, 2021, Professor Gao Tianming's research team from the School of Basic Medical Sciences, Southern Medical University, from the perspective of the plasticity of the cortical PV-ergic neuron network, explained the key process of fear memory dissipation, and further found the molecule that regulates this process: neurogulin1 -ErbB4.
Professor Tianming Gao’s team has published many high-impact factor articles this year.
The editorial department of Neuroweek K has interpreted some of these articles.
Click to view the detailed interpretation: 1.
Challenge the classics! Professor Gao Tianming reveals the differential mechanism of astrocytes and neurons in regulating synaptic plasticity 2.
Professor Gao Tianming reveals that the neural circuits that regulate anxiety and fear at the same time have different functions 3.
After ATP antidepressant, Professor Gao Tianming again One masterpiece: ATP has the potential to treat autism 4.
Li Jianming/Professor Gao Tianming reveals that the intestinal flora regulates vitamin B6 metabolism mediates autism-like behaviors to dissipate after training.
The plasticity changes of the PV neuron network after training.
Researchers successfully trained for conditioned fear The latter mice received dissipative training every 1, 2, and 3 days.
Dissipation training every 1 or 2 days can effectively reduce the expression of fear memory in mice, but after training every 3 days, Can not play the above role
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In the dissipative training, the proportion of poorly differentiated PVrgic neurons in the IL brain area increased, and the proportion of well-differentiated PVrgic neurons decreased, but this change in the plasticity of the PVrgic neuron network did not appear in the PL brain area
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Activate or inhibit PVrgic neurons to change their plasticity.
Researchers have found that chronic activation of PVrgic neurons decreases the proportion of poorly differentiated PVrgic neurons, while the proportion of well-differentiated PVrgic neurons increases.
Inhibition of PVrgic neurons has the opposite effect
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In the process of dissipating training, after artificially reducing the proportion of poorly differentiated PV-ergic neurons, the fear memory of mice dissipated obstacles
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This indicates that the formation of dissipative memory depends on the network of poorly differentiated PV-ergic neurons
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In order to further clarify the molecular mechanism that regulates the above-mentioned PV neural network, the researchers tested the known molecular level changes in the regulation of inhibitory neuron function and development after dissipative learning, of which neurogulin 1 (NRG1) has the most significant changes
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Endogenous reduction of NRG1 in IL brain regions through pharmacological means or interfering RNA technology can induce an increase in the proportion of well-differentiated PV neurons
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NRG1 exerts its function by activating ErbB tyrosine kinase, of which ErbB4 is the only one that can not only bind to NRG1 but also become a functionally active tyrosine kinase
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After inhibiting ErbB4, it can also increase the proportion of well-differentiated PV neurons
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The above results indicate that the NRG1-ErbB4 signal can regulate the plasticity of the PV-ergic neuron network
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In the process of evanescent learning, inhibiting the activity of NRG1 in the IL region or knocking down ErbB4 can hinder the formation of evanescent memory, and it can promote evanescent memory after exogenously increasing NRG1
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These results indicate that NRG1-ErbB4 signals regulate the process of fear dissipation
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Subsequent experiments found that the process of NRG1 signal regulating memory dissipation depends on changing the plasticity of the PV neuron network
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In general, the process of dissipative learning causes changes in the plasticity of the PV neuron network in the IL area (low PV energy plasticity).
The formation of this plasticity is mainly due to the increase in the expression of NRG1 in the IL area, which then activates ErbB4, which ultimately leads to highly differentiated PV The reduction in the proportion of functional neurons
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[References] 1.
Karunakaran S, Chowdhury A, Donato F, Quairiaux C, Michel CM, Caroni P.
PV plasticity sustained through D1/5 dopamine signaling required for long-term memory consolidation.
Nat Neurosci.
2016;19:454– 64.
2.
Donato, F.
, Rompani, SB & Caroni, P.
Parvalbumin-expressing basket-cell network plasticity induced by experience regulates adult learning.
Nature 504, 272–276 (2013) 3.
https://doi.
org/10.
1038 /s41380-021-01355-z The picture in the text is from the reference