Yarishkin Oleg, Lee Jaekwang, Jo Seonmi, Hwang Eun Mi, Lee C Justin
Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea. ; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.
Exp Neurobiol. 2015 Sep;24(3):211-8. doi: 10.5607/en.2015.24.3.211. Epub 2015 Sep 2.
Like neurons, astrocytes produce and release GABA to influence neuronal signaling. At the perforant path to dentate gyrus granule neuron synapse, GABA from astrocyte was found to be a strong inhibitory factor, which impairs synaptic transmission, synaptic plasticity and memory in Alzheimer's disease. Although astrocytic GABA is observed in many brain regions, its physiological role has not been clearly demonstrated yet. Here, we show that astrocytic GABA exerts disinhibitory action to dentate granule neurons by targeting GABAB receptors of GABAergic interneurons in wild-type mice. This disinhibitory effect is specific to a low intensity of electrical stimulation at perforant path fibers. Inversely in Alzheimer's disease model mice, astrocytic GABA targets GABAA receptors and exerts inhibitory action by reducing release probability of glutamatergic perforant path terminals. These results suggest that astrocytic GABA differentially modulates the signaling from cortical input to dentate gyrus under physiological and pathological conditions.
与神经元一样，星形胶质细胞产生并释放γ-氨基丁酸（GABA）以影响神经元信号传导。在穿通通路至齿状回颗粒神经元突触处，发现来自星形胶质细胞的GABA是一种强大的抑制因子，它会损害阿尔茨海默病中的突触传递、突触可塑性和记忆。尽管在许多脑区都观察到了星形胶质细胞源性GABA，但其生理作用尚未得到明确证实。在此，我们表明，在野生型小鼠中，星形胶质细胞源性GABA通过作用于GABA能中间神经元的GABAB受体，对齿状颗粒神经元发挥去抑制作用。这种去抑制作用特定于穿通通路纤维的低强度电刺激。相反，在阿尔茨海默病模型小鼠中，星形胶质细胞源性GABA作用于GABAA受体，并通过降低谷氨酸能穿通通路终末的释放概率发挥抑制作用。这些结果表明，星形胶质细胞源性GABA在生理和病理条件下对从皮质输入到齿状回的信号传导有不同的调节作用。
