Animal Physiology Group, Department of Biology, University of Kaiserslautern, D-67653 Kaiserslautern, Germany.
J Neurosci. 2012 Oct 17;32(42):14602-16. doi: 10.1523/JNEUROSCI.0765-12.2012.
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.
通过消除不合适的突触和加强合适的突触来进行突触精炼，对于建立特定的、拓扑的神经回路至关重要。驱动这些过程的机制了解甚少，特别是关于抑制性投射。在这里，我们通过涉及在最小和最大刺激、笼状谷氨酸光解和单个轴突追踪的组合中进行膜片钳记录的功能和解剖映射研究，解决了听觉脑干中抑制性拓扑投射的精炼问题。我们证明了精炼对 Ca(V)1.3 钙通道的依赖性至关重要：Ca(V)1.3(-/-) 小鼠在听觉出现之前几乎没有显示出投射的消除。此外，由于轴突末梢的数量减少，增强作用受到严重损害。中侧拓扑结构不那么精确，并且在听觉出现之前从混合 GABA/甘氨酸能传递到纯甘氨酸能传递的转变也没有发生。总之，我们的研究结果为 Ca(V)1.3 依赖性机制提供了证据，通过该机制实现了抑制性回路形成和神经递质表型的决定。
