Open AccessMesophasic organization of GABAA receptors in hippocampal inhibitory synapses
Author(s) -
Yun Tao Liu,
Chang-Lu Tao,
Xiaokang Zhang,
Wenjun Xia,
Dong-Qing Shi,
Lei Qi,
C. Shan Xu,
Runbin Sun,
Xiaowei Li,
Pak-Ming Lau,
Ziwei Zhou,
Guo-Qiang Bi
Publication year - 2020
Publication title -
nature neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 13.403
H-Index - 422
eISSN - 1546-1726
pISSN - 1097-6256
DOI - 10.1038/s41593-020-00729-w
Subject(s) - neuroscience , postsynaptic density , postsynaptic potential , inhibitory postsynaptic potential , gabaa receptor , hippocampal formation , neurotransmitter receptor , receptor , biology , synaptogenesis , chemistry , excitatory postsynaptic potential , biochemistry
Information processing in the brain depends on specialized organization of neurotransmitter receptors and scaffolding proteins within the postsynaptic density. However, how these molecules are organized in situ remains largely unknown. In this study, template-free classification of oversampled sub-tomograms was used to analyze cryo-electron tomograms of hippocampal synapses. We identified type-A GABA receptors (GABA A Rs) in inhibitory synapses and determined their in situ structure at 19-Å resolution. These receptors are organized hierarchically: from GABA A R super-complexes with a preferred inter-receptor distance of 11 nm but variable relative angles, through semi-ordered, two-dimensional receptor networks with reduced Voronoi entropy, to mesophasic assembly with a sharp phase boundary. These assemblies likely form via interactions among postsynaptic scaffolding proteins and receptors and align with putative presynaptic vesicle release sites. Such mesophasic self-organization might allow synapses to achieve a 'Goldilocks' state, striking a balance between stability and flexibility and enabling plasticity in information processing.