Center for Learning and Memory, Department of Neuroscience, The University of Texas at Austin, 1 University Station Stop, C7000, Austin, Texas, USA.
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA.
Sci Rep. 2018 Dec 3;8(1):17561. doi: 10.1038/s41598-018-35829-y.
Granule cells (GCs) in the cerebellar cortex are important for sparse encoding of afferent sensorimotor information. Modeling studies show that GCs can perform their function most effectively when they have four dendrites. Indeed, mature GCs have four short dendrites on average, each terminating in a claw-like ending that receives both excitatory and inhibitory inputs. Immature GCs, however, have significantly more dendrites-all without claws. How these redundant dendrites are refined during development is largely unclear. Here, we used in vivo time-lapse imaging and immunohistochemistry to study developmental refinement of GC dendritic arbors and its relation to synapse formation. We found that while the formation of dendritic claws stabilized the dendrites, the selection of surviving dendrites was made before claw formation, and longer immature dendrites had a significantly higher chance of survival than shorter dendrites. Using immunohistochemistry, we show that glutamatergic and GABAergic synapses are transiently formed on immature GC dendrites, and the number of GABAergic, but not glutamatergic, synapses correlates with the length of immature dendrites. Together, these results suggest a potential role of transient GABAergic synapses on dendritic selection and show that preselected dendrites are stabilized by the formation of dendritic claws-the site of mature synapses.
小脑皮层中的颗粒细胞 (GCs) 对于传入感觉运动信息的稀疏编码很重要。建模研究表明，GC 具有四个树突时可以最有效地发挥其功能。事实上，成熟的 GCs 平均有四个短的树突，每个树突末端都有一个爪状的末梢，接收兴奋性和抑制性输入。然而，不成熟的 GCs 有明显更多的树突——所有这些树突都没有爪子。这些多余的树突在发育过程中是如何细化的，在很大程度上还不清楚。在这里，我们使用体内延时成像和免疫组织化学来研究 GC 树突棘的发育细化及其与突触形成的关系。我们发现，虽然树突爪的形成稳定了树突，但存活树突的选择是在形成爪之前做出的，并且较长的不成熟树突比较短的树突有更高的存活机会。通过免疫组织化学，我们表明谷氨酸能和 GABA 能突触在不成熟的 GC 树突上短暂形成，并且 GABA 能突触的数量而不是谷氨酸能突触的数量与不成熟树突的长度相关。这些结果表明，瞬态 GABA 能突触在树突选择中可能起作用，并表明预先选择的树突通过树突爪的形成而稳定，而树突爪是成熟突触的位置。
