Neuron: It hurts to breathe!

Click on the blue word to pay attention to our intense and uncontrollable pain that can cause excessive breathing
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In a state of fear and post-traumatic stress disorder, the breathing rhythm becomes deeper and shallower
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The pontine breathing group, which controls breathing rhythm, is located at the head of the pontine, including structures such as the parabrachial nucleus (PB).
There are more expiratory neurons, and it integrates emotional and sensory information input
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Studies have shown that activation of dorsal PB causes shortness of breath, while activation of ventral PB causes apnea and slow breathing
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The lateral PB transmits pain signals from the spinal cord to the forebrain, and the lateral PB neurons express the gene Oprm1, which encodes the μ-opioid receptor
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Oprm1 knockout mice can block the analgesic effect of morphine
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On December 17, 2021, the Sung Han research team at the Salk Institute for Biological Research in California, USA, discovered that the neurons expressing Oprm1 in the lateral parabrachial nucleus simultaneously control breathing, pain and anxiety
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Figure 1: Changes in respiratory behavior after activating or inhibiting PBL-Oprm1 neurons Increase, while other types of neurons in the lateral PB brain area do not encode behavioral information related to breathing
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Chemical activation of Oprm1rgic neurons in the lateral PB brain area (hereinafter referred to as PBL-Oprm1 neurons) can increase the respiratory rate of mice, and decrease the respiratory rate after inhibiting this type of neurons (Figure 1)
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More interestingly, single-cell level calcium imaging technology found that most PBL-Oprm1 neurons respond to pain and respiration at the same time.
Specifically, 62% of neurons respond at the same time, 14.
8% of neurons respond only to respiration, and 21.
3% Neurons respond only to pain
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Figure 2: The upstream input of the PBL-Oprm1 neuron retrograde tracer virus reveals that the PBL-Oprm1 neuron receives from the central nucleus of the amygdala (CeA), the stria terminalis (BNST), the inferior parafascicular nucleus in the posterior thalamus, Inputs from the superior colliculus (SC), nucleus tractus solitarius (NTS), and spinal cord (Figure 2)
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The anterograde tracer virus found that PBL-Oprm1 neurons projected to the hypothalamus, CeA, BNST, preBotC and other brain regions
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preBotC is considered to be the origin of breathing rhythm
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Chemical genetics activates PBL-Oprm1 neurons to project to the loop of preBotC and increases the mouse's respiratory rate
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After touching the tail with a hot rod at 55 degrees Celsius or pressing the tail with a 300g weight to produce harmful painful stimuli, the breathing rate of the mice was significantly increased, and at the same time the calcium ion activity of PBL-Oprm1 neurons was significantly increased
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Light inhibition of the above-mentioned neurons can alleviate the increase in breathing caused by painful stimuli
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Because PBL-Oprm1 neurons interact with the brain regions CeA and BNST that regulate emotion and pain, the researchers speculate that PBL-Oprm1 neurons may be involved in pain and anxiety behaviors
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Subsequent experiments confirmed this hypothesis: inhibiting the activity of PBL-Oprm1 neurons can effectively alleviate the pain caused by the plantar electric shock, and it can also promote the mice to stay more in the open arms of the elevated experiment
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Figure 3: The "core-shell" structure formed by the PBL-Oprm1 neuron group.
From the anatomical shape, PBL-Oprm1 neurons project to CeA (PBL→CeA) and PBL-Oprm1 neurons project to preBotC (PBL→ preBotC) forms a “core-shell” structure similar to the NAc brain area, where PBL→CeA forms a core structure, and PBL→preBotC forms a shell structure (Figure 3)
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Further experiments showed that after light-activated neurons in the core or shell area of ​​the PBL, the mouse's breathing rate increased, aggravated pain (the number of jumps on the high temperature board was increased), and the mouse's stay time in the open arm was reduced (to promote anxiety)
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Inhibiting neurons in the core area or the shell area can reduce the respiratory rate.
The difference is that inhibiting the core area can relieve pain and increase the residence time of the mouse in the open arm (anti-anxiety), but inhibiting the neurons in the shell area does not These effects
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These results indicate that neurons in the core area and shell area of ​​PBL regulate breathing and pain emotions through different degrees and different activities (activation or inhibition)
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In summary, this article reveals that there is a group of neurons in the parabrachial nucleus that simultaneously regulate negative emotions such as breathing and pain: PBL-Oprm1 neurons.
This type of neuron group forms a ``core-shell'' structure.
Projected to the forebrain and hindbrain regions respectively play different roles
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[References] 1.
https://doi.
org/10.
1016/j.
neuron.
2021.
11.
029 The pictures in the article are from the references