Missler M, Wolff A, Merker H J, Wolff J R
Department of Anatomy, University of Göttingen, Germany.
J Comp Neurol. 1993 Jul 1;333(1):53-67. doi: 10.1002/cne.903330105.
During ontogenesis changes in the numerical density of synapses are usually assumed to depend essentially on variations in the formation of synapses. Only the final adjustment to adult synapse densities is thought to include the elimination of synapses in some brain regions of certain species. Here, we focus attention on quantitative aspects of synapse elimination throughout development of area 17 of marmoset monkeys (Callithrix jacchus). Mature synapses, various precursor forms, and indicators of lysosomal degradation of synapses were quantitatively analysed by electron microscopy and morphometric methods. A total number of about 135 x 10(9) synapses was calculated for area 17 in each adult hemisphere corresponding to a volume density of 600 x 10(6) synapses/mm3. At 3 months of age, the respective values were 508 x 10(9)/area and 1,159 x 10(6)/mm3, while at birth these values were 69 x 10(9)/area and 328 x 10(6)/mm3. Consequently, at least three out of four synapses are eliminated between 3 months and adulthood. However, the real number of synapses being eliminated during development is probably much larger if the time course of lysosomal degradation is additionally taken into account. The frequency of lysosomes in presynaptic endings is highest before net-elimination of synapses occurs, i.e., between 1 and 3 months. This suggests that lysosomal degradation is not directly responsible for the majority of synapses removed during ontogenesis but apparently represents a second mechanism for synapse remodelling and elimination. Thus, it appears from this study that remodelling and elimination of synapses are quantitatively as important as their formation, and accompany synaptogenesis from its very onset onwards.
在个体发育过程中,通常认为突触数量密度的变化主要取决于突触形成的变化。只有对成年突触密度的最终调整才被认为包括某些物种特定脑区中突触的消除。在这里,我们关注狨猴(Callithrix jacchus)第17区整个发育过程中突触消除的定量方面。通过电子显微镜和形态计量学方法对成熟突触、各种前体形式以及突触溶酶体降解指标进行了定量分析。每个成年半球的第17区计算出的突触总数约为135×10⁹个,对应体积密度为600×10⁶个突触/mm³。在3个月大时,相应的值分别为508×10⁹/区和1159×10⁶/mm³,而出生时这些值分别为69×10⁹/区和328×10⁶/mm³。因此,在3个月到成年之间,至少四分之三的突触被消除。然而,如果额外考虑溶酶体降解的时间进程,发育过程中实际被消除的突触数量可能要多得多。突触前终末中溶酶体的频率在突触净消除之前最高,即在1到3个月之间。这表明溶酶体降解并非个体发育过程中大多数被去除突触的直接原因,但显然代表了突触重塑和消除的第二种机制。因此,从这项研究来看,突触的重塑和消除在数量上与其形成同样重要,并且从突触发生一开始就伴随着它。