Hoon Mrinalini, Sinha Raunak, Okawa Haruhisa, Suzuki Sachihiro C, Hirano Arlene A, Brecha Nicholas, Rieke Fred, Wong Rachel O L
Department of Biological Structure, University of Washington, Seattle, WA 98195;
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195;
Proc Natl Acad Sci U S A. 2015 Oct 13;112(41):12840-5. doi: 10.1073/pnas.1510483112. Epub 2015 Sep 29.
Neuronal output is modulated by inhibition onto both dendrites and axons. It is unknown whether inhibitory synapses at these two cellular compartments of an individual neuron are regulated coordinately or separately during in vivo development. Because neurotransmission influences synapse maturation and circuit development, we determined how loss of inhibition affects the expression of diverse types of inhibitory receptors on the axon and dendrites of mouse retinal bipolar cells. We found that axonal GABA but not glycine receptor expression depends on neurotransmission. Importantly, axonal and dendritic GABAA receptors comprise distinct subunit compositions that are regulated differentially by GABA release: Axonal GABAA receptors are down-regulated but dendritic receptors are up-regulated in the absence of inhibition. The homeostatic increase in GABAA receptors on bipolar cell dendrites is pathway-specific: Cone but not rod bipolar cell dendrites maintain an up-regulation of receptors in the transmission deficient mutants. Furthermore, the bipolar cell GABAA receptor alterations are a consequence of impaired vesicular GABA release from amacrine but not horizontal interneurons. Thus, inhibitory neurotransmission regulates in vivo postsynaptic maturation of inhibitory synapses with contrasting modes of action specific to synapse type and location.
神经元输出通过对树突和轴突的抑制作用进行调节。在个体神经元的这两个细胞区室中，抑制性突触在体内发育过程中是协同调节还是分别调节尚不清楚。由于神经传递会影响突触成熟和神经回路发育，我们研究了抑制作用的丧失如何影响小鼠视网膜双极细胞轴突和树突上不同类型抑制性受体的表达。我们发现轴突上的GABA受体表达而非甘氨酸受体表达依赖于神经传递。重要的是，轴突和树突上的GABAA受体具有不同的亚基组成，它们受GABA释放的差异调节：在缺乏抑制作用时，轴突上的GABAA受体下调，而树突上的受体上调。双极细胞树突上GABAA受体的稳态增加具有通路特异性：在传递缺陷型突变体中，视锥双极细胞而非视杆双极细胞的树突维持受体上调。此外，双极细胞GABAA受体的改变是无长突细胞而非水平中间神经元的囊泡GABA释放受损的结果。因此，抑制性神经传递以特定于突触类型和位置的不同作用模式调节体内抑制性突触的突触后成熟。
