Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
Neuron. 2018 May 16;98(4):718-725.e3. doi: 10.1016/j.neuron.2018.03.046. Epub 2018 Apr 26.
While the canonical assembly of a GABA receptor contains two α subunits, two β subunits, and a fifth subunit, it is unclear which variants of each subunit are necessary for native receptors. We used CRISPR/Cas9 to dissect the role of the GABA receptor β subunits in inhibitory transmission onto hippocampal CA1 pyramidal cells and found that deletion of all β subunits 1, 2, and 3 completely eliminated inhibitory responses. In addition, only knockout of β3, alone or in combination with another β subunit, impaired inhibitory synaptic transmission. We found that β3 knockout impairs inhibitory input from PV but not SOM expressing interneurons. Furthermore, expression of β3 alone on the background of the β1-3 subunit knockout was sufficient to restore synaptic and extrasynaptic inhibitory transmission. These findings reveal a crucial role for the β3 subunit in inhibitory transmission and identify a synapse-specific role of the β3 subunit in GABAergic synaptic transmission.
虽然 GABA 受体的规范组装包含两个 α 亚基、两个 β 亚基和一个第五亚基，但对于天然受体，哪些亚基变体是必需的尚不清楚。我们使用 CRISPR/Cas9 来剖析 GABA 受体 β 亚基在海马 CA1 锥体神经元抑制性传递中的作用，发现所有 β 亚基 1、2 和 3 的缺失完全消除了抑制性反应。此外，只有 β3 的敲除，单独或与另一个 β 亚基一起，损害了抑制性突触传递。我们发现，β3 敲除损害了来自 PV 但不是 SOM 表达中间神经元的抑制性输入。此外，在 β1-3 亚基敲除的背景下单独表达 β3 足以恢复突触和 extrasynaptic 抑制性传递。这些发现揭示了 β3 亚基在抑制性传递中的关键作用，并确定了 β3 亚基在 GABA 能突触传递中的突触特异性作用。
