Optogenetic activation of dorsal hippocampal astrocytic Rac1 blocks the learning of associative memory
- Author:
- No author available
- Journal Title:
- Acta Physiologica Sinica
- Issue:
- 3
- DOI:
- 10.13294/j.aps.2017.0031
- Key Word:
- 光激活Rac1;星形胶质细胞;光激活;关联性学习;photoactivatable analogue of Rac1;astrocyte;optogenetic activation;associative learning
Abstract： Rac1 belongs to the family ofRho GTPases,and plays important roles in the brain function.It affects the cell migration and axon guidance via regulating the cytoskeleton and cellular morphology.However,the effect of its dynamic activation in regulating physiological function remains unclear.Recently,a photoactivatable analogue of Rac1 (PA-Rac1) has been developed,allowing the activation of Rac 1 by the specific wavelength of light in living cells.Thus,we constructed recombinant adeno-associated virus (AAV) of PA-Rac1 and its light-insensitive mutant PA-Rac1-C450A under the control of the mouse glial fibrillary acidic protein (mGFAP) promoter to manipulate Rac1 activity in astrocytes by optica1 stimulation.Primary culture of hippocampal astrocytes was infected with the recombinant AAV-PA-Rac1 or AAV-PA-Rac1-C450A.Real-time fluorescence imaging showed that the cell membrane of the astrocyte expressing PA-Rac1 protruded near the light spot,while the astrocyte expressing PA-Rac1-C450A did not.We injected AAV-PA-Rac1 and AAV-PA-Rac1-C450A into dorsal hippocampus to investigate the role of the activation of Rac1 in regulating the associative learning.With optical stimulation,the PA-Rac1 group,rather than the PA-Rac1-C450A group,showed slower learning curve during the fear conditioning compared with the control group,indicating that activating astrocytic Rac1 blocks the formation of contextual memory.Our data suggest that the activation of Rac1 in dorsal hippocampal astrocyte plays an important role in the associative learning.
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