The elucidation of developmental synaptic elimination mechanisms using in vivo patch-clamp methods and two-photon imaging

功能性神经回路的发育涉及到多余突触连接的初始形成，随后是必要突触的加强和多余突触的消除。神经元活动如何促进这一发育过程仍不清楚。采用全细胞记录和双光子Ca^<2+>成像技术，研究了发育大鼠完整小脑内攀爬纤维-浦肯野细胞突触的活性。我们发现，未成熟PC的突发峰值（BS）需要多个CF输入的总和。重要的是，在BS发病前的CF-EPSP在出生后的发育中有选择性地增强。由于BS在pc中引起Ca^<2+>瞬变，因此与BS诱导的Ca^<2+>升高同步的CF-EPSP似乎被增强了。因此，涉及同步CF输入和突触后Ca^<2+>升高的峰值时间依赖机制似乎是单个CF的选择和单个pc中成熟CF- pc连接建立的基础。

Development of functional neuronal circuits involves initial formation of supernumerary synaptic connections followed by strengthening of necessary synapses and elimination of redundant ones in early postnatal life. How neuronal activity contributes to this developmental process still remains unknown. We examined activities of Climbing-fiber(CF)-Purkinje cell(PC) synapses in intact cerebellum of developing rat by in vivo whole-cell recordings and two-photon Ca^<2+> imaging. We found that burst spiking (BS) of immature PC required summation of multiple CF inputs. Importantly the CF-EPSP just before the BS onset was selectively strengthened during postnatal development. Since BS elicited Ca^<2+> transients in PCs, the CF-EPSP synchronous to the BS-induced Ca^<2+> rise appeared to be potentiated. Thus, spike timing-dependent mechanisms involving synchronous CF inputs and postsynaptic Ca^<2+> elevation appear to underlie the selection of single CFs and the establishment of mature CF-PC connections in individual PCs.