Axon overproduction and elimination in the corpus callosum of the developing rhesus monkey

Abstract

We have studied the cytological and quantitative aspects of axon addition and elimination in the corpus callosum of the developing rhesus monkey. Electron microscopic analysis reveals that during fetal development the number of callosal axons increases from 4 million at embryonic day 65 (E65) to 188 million at birth (E 165). Thus, the number of callosal axons in newborn monkeys exceeds the number present in the adult (an average of 56 million; LaMantia and Rakic, 1990a) by at least 3.5 times. Although there is some variability among the 11 fetal and newborn monkeys examined, there appears to be a progressive increase in the total number of callosal axons from midgestation through birth. The presence and numbers of growth cones from E65 through birth suggests that axon addition occurs exclusively during this period. There is no ultrastructural or quantitative indication of postnatal axon addition. After birth, about 70% of the axons in the callosum are eliminated in 2 phases. During the first phase, which includes the first 3 postnatal weeks, approximately 80 million axons are lost at an estimated rate of 4.4 million/d or 50/sec. During the second phase, which continues for the following 3 months, an additional 50 million axons are eliminated at a rate of 0.5 million/d or 5/sec until the adult value is reached. A discontinuous distribution of different classes of axons along the anterior-posterior axis of the tract reminiscent of the pattern seen in the adult is detectable before the onset of the first phase of axon elimination. Since the basic topography and terminal field patterns of callosal projections are well established before birth in all regions of the monkey cortex examined so far (Goldman-Rakic et al., 1983; Killackey and Chalupa, 1986; Dehay et al., 1988; Schwartz and Goldman-Rakic, 1990), we conclude that the massive postnatal elimination of callosal axons described here is unlikely to play a significant role in the development of discretely patterned callosal projection zones or their columnar terminations. The coincidence of axon elimination and the increase in synaptic density throughout the primate cerebral cortex during the first 6 postnatal months (Rakic et al., 1986), however, suggests that supernumerary axons may be lost during a process that results in the local proliferation of synapses from a subset of initial interhemispheric projections.

Development of white matter and reading skills

“…During development, some axons grow, and other axons are eliminated in a process called "pruning" (35,36). LaMantia and Rakic (35) demonstrated that a rhesus monkey's corpus callosum contains 3.5 times more axons at birth than in adulthood. The pruning process also is driven in part by experience (37).…”

The Crossed Projection to the Striatum in Two Species of Monkey and in Humans: Behavioral and Evolutionary Significance

“…Cortical connectivity, in particular callosal connectivity, is exuberant (i.e., more diffuse) in early development (reviewed in Innocenti and Price 2005), a concept that specifically applies to primates where exuberant projections were described in several structures, notably the corpus callosum (Chalupa and Killackey 1989;LaMantia and Rakic 1990). The existence of differences between monkeys and humans such as those mentioned above seems to indicate that the sculpting out of the initially exuberant, juvenile callosal connections undergoes species-specific regulation in development, apparently attuned to the emergence of language.…”

Schizophrenia, neurodevelopment and corpus callosum

“…22,23 Animal studies have shown that cortical connections develop through phases of exuberant growth, followed by partial regression. Initially both long-and local axonal branches are formed in excess and, subsequently, massive elimination of axonal branches takes place [24][25][26][27][28][29][30][31][32][33] (see also Innocenti 34 for a review). This regressive phase is concomitant with synaptogenesis, which eventually leads to the overproduction of synapses that are subsequently deleted.…”

“…The advantage of these connections is that unlike the other cortico-cortical connections, they can be investigated morphologically, physiologically and neuropsychologically. They are also the only cortical connections for which rather complete developmental data exist, including the quantitative estimates of axonal elimination in normal development in cat, 16,28 monkey, 30 and by inference in man. 70 The differentiation of the terminal arbor of callosal axons has also been studied in detail and a number of developmental stages have been identified.…”