Institute for Integrative Neuroanatomy, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Cereb Cortex. 2019 Mar 1;29(3):1230-1243. doi: 10.1093/cercor/bhy029.
In the mammalian cortex, GABAergic and glutamatergic neurons represent 2 major neuronal classes, which establish inhibitory and excitatory synapses, respectively. Despite differences in their anatomy, physiology and developmental origin, both cell types require support from glial cells, particularly astrocytes, for their growth and survival. Recent experiments indicate that glutamatergic neurons also depend on astrocytes for synapse formation. However, it is not clear if the same holds true for GABAergic neurons. By studying highly pure GABAergic cell cultures, established through fluorescent activated cell sorting, we find that purified GABAergic neurons are smaller and have reduced survival, nevertheless they establish robust synaptic transmission in the absence of glia. Support from glial cells reverses morphological and survival deficits, but does little to alter synaptic transmission. In contrast, in cultures of purified glutamatergic neurons, morphological development, survival and synaptic transmission are collectively dependent on glial support. Thus, our results demonstrate a fundamental difference in the way GABAergic and glutamatergic neurons depend on glia for the establishment of synaptic transmission, a finding that has important implications for our understanding of how neuronal networks develop.
在哺乳动物大脑皮层中,GABA 能神经元和谷氨酸能神经元分别代表了两种主要的神经元类型,它们分别建立抑制性和兴奋性突触。尽管它们在解剖学、生理学和发育起源上存在差异,但这两种细胞类型的生长和存活都需要神经胶质细胞的支持,特别是星形胶质细胞。最近的实验表明,谷氨酸能神经元的突触形成也依赖于星形胶质细胞。然而,对于 GABA 能神经元是否也是如此还不清楚。通过研究通过荧光激活细胞分选建立的高度纯 GABA 能细胞培养物,我们发现纯化的 GABA 能神经元体积较小,存活减少,但在没有神经胶质细胞的情况下仍能建立强大的突触传递。神经胶质细胞的支持可以逆转形态和存活缺陷,但对突触传递影响不大。相比之下,在纯化的谷氨酸能神经元培养物中,形态发育、存活和突触传递都依赖于神经胶质细胞的支持。因此,我们的结果表明 GABA 能和谷氨酸能神经元在建立突触传递方面对神经胶质细胞的依赖方式存在根本差异,这一发现对我们理解神经元网络的发育方式具有重要意义。