Synaptic Refinement of an Inhibitory Topographic Map in the Auditory Brainstem Requires Functional CaV1.3 Calcium Channels
Synaptic Refinement of an Inhibitory Topographic Map in the Auditory Brainstem Requires Functional CaV1.3 Calcium Channels
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DOI：
10.1523/jneurosci.0765-12.2012
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发表时间：
2012-10-17
影响因子：
5.3
通讯作者：
Friauf, Eckhard
中科院分区：
文献类型：
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作者：
Hirtz, Jan J.;Braun, Nadine;Friauf, Eckhard
通过消除不适当的突触和加强适当的突触来细化突触对于建立特定的拓扑神经回路至关重要。驱动这些过程的机制知之甚少，特别是关于抑制性投射。在这里，我们解决了细化的抑制性地形投影在听觉脑干的功能和解剖映射研究，包括膜片钳记录结合最小和最大的刺激，笼状谷氨酸光解，和单轴突追踪。我们证明了对Ca（V）1.3钙通道的精细化的关键依赖性：Ca（V）1.3（-/-）小鼠在听力发作之前几乎没有显示出消除投射。此外，加强强烈受损，与轴突终扣数量减少一致。中外侧地形是不太精确的，从混合GABA/甘氨酸传输到纯甘氨酸传输听力发作前没有发生的转变。总之，我们的研究结果提供了Ca（V）1.3依赖性机制的证据，通过该机制，实现了抑制回路的形成和神经递质表型的确定。
Synaptic refinement via the elimination of inappropriate synapses and strengthening of appropriate ones is crucially important for the establishment of specific, topographic neural circuits. The mechanisms driving these processes are poorly understood, particularly concerning inhibitory projections. Here, we address the refinement of an inhibitory topographic projection in the auditory brainstem in functional and anatomical mapping studies involving patch-clamp recordings in combination with minimal and maximal stimulation, caged glutamate photolysis, and single axon tracing. We demonstrate a crucial dependency of the refinement on Ca(V)1.3 calcium channels: Ca(V)1.3(-/-) mice displayed virtually no elimination of projections up to hearing onset. Furthermore, strengthening was strongly impaired, in line with a reduced number of axonal boutons. The mediolateral topography was less precise and the shift from a mixed GABA/glycinergic to a purely glycinergic transmission before hearing onset did not occur. Together, our findings provide evidence for a Ca(V)1.3-dependent mechanism through which both inhibitory circuit formation and determination of the neurotransmitter phenotype are achieved.