Neuron: It hurts to look at?

Click on the blue word to pay attention to our empathy behavior is common in mammals, and this behavior is different between different species, and its manifestations are also diverse
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Emotions such as happiness, pain, stress, and fear can all be transmitted among peers in the form of empathy
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Multiple brain regions are involved in empathic pain behavior: damage to the prefrontal cortex impairs the formation of empathic pain behavior; anterior cingulate cortex mirror neurons increase activity in empathic pain behavior; nucleus accumbens-anterior cingulate cortex neural loop The circuit is activated in empathic pain behavior, and inhibition of this circuit can relieve pain
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On April 19, 2022, in the journal Neuron, the research team of Chen Tao from Fourth Military Medical University revealed the circuit and molecular mechanism of empathic pain behavior with cerebral hemisphere laterality
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Figure 1: Bystander pain behavior flow The researchers established a bystander pain behavior model: bystander mice and left common peroneal nerve ligation pain model mice were placed in a mouse cage separated by a plastic plate
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Bystander mice developed marked allodynia during the training period, which persisted for 2 weeks, during which time neurons in the right insular cortex (IC) and basolateral amygdala (BLA) of the bystander mice were activated most neurons
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Further virus tracing experiments found that excitatory neurons in the IC area can project anterogradely to the BLA, and the IC area can receive retrograde projections from the BLA area, which indicates that there is a direct anatomical connection projection from IC to BLA
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Figure 2: Chemogenetics modulates the IC→BLA circuit.
Chronic activation of the IC→BLA circuit by chemogenetics produces a transient pain response in normal mice, while inhibition of this circuit in bystander mice relieves pain.
behavior, suggesting that this neural circuit regulates empathic pain behavior
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Through in vitro electrophysiological experiments, it was found that during empathic pain behavior, the excitatory postsynaptic currents of circuit neurons in bystander mice increased, the release of presynaptic glutamate increased, and pyramidal neurons in the IC projecting BLA brain regions and Excitatory inputs to interneurons are all increased
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 Figure 3: Virus-induced apoptosis of internergic neurons Further use of a virus strategy to specifically induce pyramidal neurons in the BLA brain region reduces pain in bystander mice, while after inducing death of internergic neurons (Figure 3), bystander mice are aggravated The pain response of the mice in the control group showed that the IC→BLA loop postsynaptic pyramidal neurons and interergic neurons play different roles in empathic pain behavior: the former mediates the expression of empathic pain, and the latter participates in empathic pain behavior.
The intensity of empathic pain
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In order to further find the molecular mechanism of synaptic regulation of pain empathy behavior, they found by RNA sequencing that the IC and BLA regions of bystander mice were enriched in the expression of genes related to synaptic transmission, among which synaptotagmin-2 (regulatory presynaptic vesicle transport and Exocytosis and regulation of vesicle release) and RIM3 (distributed in the postsynaptic region and involved in synaptic transmission) were enriched and up-regulated
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Virus-specific reduction of synaptotagmin-2 or RIM3 expression on the IC→BLA loop significantly reduced presynaptic glutamate release and improved pain responses in bystander mice, indicating that presynaptic synaptotagmin-2 and postsynaptic The protein RIM3 regulates the IC→BLA loop synaptic transmission process of pain empathy behavior
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The anterior cingulate cortex is a key brain region that regulates empathic behavior
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Using in vivo electrophysiological techniques, the researchers found that on the first day of the training period, the firing activity of the anterior cingulate cortex neurons of the bystander mice was significantly enhanced, and the enhancement of this firing activity gradually weakened or even disappeared after the seventh day
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From day 1 to day 7 of the training period, the neuronal firing activity in the IC area continued to increase, which indicated that the anterior cingulate cortex was involved in the formation of empathic pain behavior, while the IC brain area was involved in the formation and consolidation of empathic pain behavior
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Collectively, this paper sheds light on the neural circuits and synaptic modulation mechanisms of pain empathic behavior: enhanced glutamatergic synaptic transmission from the right insular cortex projecting to the right basolateral amygdala circuit, this enhanced Depends on the synaptic proteins synaptotagmin-2 and RIM3
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[References] 1.
https://doi.
org/10.
1016/j.
neuron.
2022.
03.
030 The pictures in the text are from the references