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Natural selection, survival of the fittest
.
As the main behavior of species adapting to the environment, the struggle for survival has played an important role in the long process of biological evolution
On January 3, 2022, Cao Peng's research group from Beijing Institute of Biological Sciences / Tsinghua University Interdisciplinary Institute of Biomedical Sciences published an online paper titled Mechanicallyevoked defensive attack is controlled by GABAergic neurons in the anterior in Nature Neuroscience, a well-known journal in neuroscience.
Research paper on hypothalamicnucleus
Nociceptive mechanical stimuli are key stimuli that trigger defensive-aggressive behavior in mice
First, the authors conducted a series of behavioral experiments using C57BL/6 mice to explore the key stimuli (keystimulus) that trigger defensive aggressive behavior
.
First, the authors applied snake odor to the simulated snake to provide olfactory information of natural enemies, or attached alligator clips to apply noxious mechanical stimuli
vGAT+ AHN neurons are necessary to trigger defensive-aggressive behavior in mice
The authors then looked for the central mechanism of defense against aggressive behavior
.
Using fluorescence in situ hybridization (FISH), they found that the neuron types in the AHN brain region were mainly vGAT-positive neurons
vGAT+ AHN neurons encode strength and location of mechanical stimulation
To reveal the link between vGAT+ AHN neurons and noxious mechanical stimulation, the authors used a calcium imaging fiber optic recording system to inject AAV-DIO-GCaMP7 into the AHN brain region of vGAT-IRES-Cre mice, and observed vGAT+ AHN neurons in the AHN brain region.
Calcium signals under different stimuli in different scenarios
.
Free-moving mice showed a large increase in calcium signal after the tail was "bited" by alligator clips, and in other scenarios (such as free-motion or exploration), the calcium signal of vGAT+ AHN neurons was slightly increased in amplitude
Next, the authors applied in vivo single-cell recording technology to deeply analyze the encoding mechanism of single vGAT+ AHN neurons for mechanical stimulation
.
AAV-DIO-ChR2-mCherry was injected into the AHN brain region of vGAT-IRES-Cre mice.
Monosynaptic afferents upstream of vGAT+ AHN neurons
To understand the sources of information encoded by vGAT+ AHN neurons to noxious mechanical stimuli, we reconstructed the upstream projection network of vGAT+ AHN neurons using Rabies Virus transsynaptic retrograde tracing
.
They found that vGAT+ AHN neurons form monosynaptic connections with brain regions that process pain-related information, such as the LPB and PVT
Photoactivation of vGAT+ AHN neurons can trigger defensive-aggressive behavior in mice
Next, the authors used optogenetics to further test whether vGAT+ AHN neurons are sufficient conditions for defense against aggressive behavior
.
AAV-DIO-ChR2-mCherry was injected into the AHN brain region of vGAT-IRES-Cre mice and the fiber was embedded, and then a series of behavioral studies were performed
The vGAT+ AHN-vlPAG pathway is necessary and sufficient to trigger defensive aggressive behavior in mice
In order to study the circuit mechanism of vGAT+ AHN neurons regulating defensive-aggressive behavior, the authors first used the SynaptoTag anterograde tracing method, injected AAV-DIO-SynaptoTag into the AHN of vGAT-IRES-Cre mice, and found that vGAT+ AHN neurons The downstream projections include the preoptic medial area MPA, the lateral phrenic nucleus LS, the medial hypothalamus ventral area VMH, the dorsal area of the prepapillary nucleus PMD, and the ventrolateral periaqueductal gray area vlPAG,
etc.
Both vlPAG and LS are known to be involved in attack-related behaviors, so the authors conducted a comparative study of the vGAT+ AHN-vlPAG and vGAT+ AHN-LS pathways
.
By activating vGAT+ AHN neuronal fiber terminals projecting to vlPAG and LS, it was found that activation of the vGAT+ AHN-vlPAG pathway can effectively trigger defensive-aggressive behavior in mice, while the vGAT+ AHN-LS pathway does not
.
The above experimental results demonstrate that the defensive-aggressive behavior of mice depends on the inhibitory synaptic connection between AHN and vlPAG
.
Finally, the authors validated the vGAT+AHN-vlPAG pathway using a dual approach of optogenetic inhibition and chemogenetic inhibition
.
The authors found that inhibiting the axonal terminals of vGAT+ AHN neurons projecting to vlPAG by the above method significantly blocked the generation of defensive-aggressive behavior
.
These results suggest that activation of the vGAT+AHN-vlPAG pathway is a sufficient and necessary condition to trigger defensive aggressive behavior in mice
.
Xie Zhiyong, Gu Huating, and Huang Meizhu from Cao Peng's lab are the co-first authors of the research paper
.
Other members of the laboratory (Cheng Xinyu, Shang Congping, Tao Ting, Li Dapeng) also made important contributions to this research
.
Zhang Zhibin's laboratory of the Institute of Zoology, Chinese Academy of Sciences, Zhang Fan's laboratory of Hebei Medical University, Tang Zongxiang's laboratory of Nanjing University of Traditional Chinese Medicine, and Zhancheng's laboratory of our institute also participated in this project and made important contributions
.
The research paper was heavily funded by the Beijing Institute of Life Sciences and the National Natural Science Foundation of China
.
Paper link: https:// Fanselow, MS & Lester, LS Afunctional behavioristic approach to aversively motivated behavior: Predatory imminence as a determinant of the topography of defensive behavior.
Evolution and Learning, 185-211 (1988).
