Distribution of corticospinal motor neurons in the postnatal rat: Quantitative evidence for massive collateral elimination and modest cell death

Abstract

The postnatal development of rat corticospinal motor neurons (CSMN) was studied by retrograde tracing with cholera toxin B subunit (CTB) injected into the upper cervical dorsal spinal cord on the first postnatal day (P0), P3, P10, P20, and at adulthood. CTB-labeled neurons were visualized by immunocytochemistry and extensively quantified throughout the cortex. At P0, CSMN were found to an extent similar to that reported in P3 animals with other neuronal tracers, now permitting in vitro studies of neonatal CSMN. Between P0 and P3, the number of labeled neurons increased by 30% to a total maximum of approximately 185,000 in both cortices. The increase occurred throughout the cortex. At P10, the number of labeled CSMN had decreased to 60% of the number at P3. Fewer CSMN were evident particularly in the perirhinal cortex. Between P10 and P20, the number of CSMN decreased further to 52% of the maximal number at P3. This decrease occurred predominantly in the cingulate and parietal cortex. The number of labeled CSMN in rats injected at P0 and analyzed at P20 was 10% lower than the number in P0-injected littermates that were analyzed at P3, which suggests that only a small portion of the "disappearing" CSMN undergoes developmental neuronal death. Thus, the spinal projection of the remaining 38% is apparently eliminated between P3 and P20. Detailed quantitative analysis of the CSMN distribution demonstrated that neuronal death occurs predominantly in the perirhinal cortex. In contrast, axonal elimination of corticospinal projections occurred throughout the CSMN field, i.e., primarily in the frontal, occipital, and perirhinal cortex between P3-P10 and in the cingulate and parietal cortex between P10-P20.

A Retrograde Tracing Study of Compensatory Corticospinal Projections in Rats with Neonatal Hemidecortication

“…Except for those originating in the SMC, the developmental corticospinal tract axons that temporarily project from the pyramidal neurons throughout the entire cerebral cortex are eliminated, although the neurons themselves persist. In addition, neuronal apoptosis might occur during the developmental period [33]. …”

Endogenous Brain-Derived Neurotrophic Factor and Neurotrophin-3 Antagonistically Regulate Survival of Axotomized Corticospinal NeuronsIn Vivo

“…For this analysis, it is necessary to specifically label CSNs by injecting retrograde tracers to the corticospinal tract of the spinal cord. Because homozygous BDNF (Ernfors et al, 1994a;Jones et al, 1994) and NT-3 knock-out mice (Ernfors et al, 1994b;Tessarollo et al, 1994) survive only a few days after birth, and the axonal connectivity of CSNs to the spinal cord develops between P0 and P20 (Jones et al, 1982;Oudega et al, 1994;Uematsu et al, 1996), only the respective heterozygous (ϩ/Ϫ) and wild-type (ϩ/ϩ) animals were analyzed. CSNs were labeled with RDX in 6-week-old mice.…”

The Change of Intra-cerebral CST Location during Childhood and Adolescence; Diffusion Tensor Tractography Study

“…Oudega et al (1994) reported in rat model that early in development, corticospinal neurons are distributed throughout much of the frontal and parietal lobes, but their distribution is later restricted to the posterior frontal and parietal lobes. In 2009, by diffusion tensor imaging (DTI) study by Kumar et al (2009) reported about origin and course of the CST in 42 healthy children.…”

“…Several previous studies reported that CST with different cerebral origin has different characteristics of the motor function, but most studies were postmortem studies which investigated animal brain instead of human brain (Russell and Demyer, 1961; Galea and Darian-Smith, 1994; Oudega et al, 1994; Maier et al, 1997; Dum and Strick, 2002; Martin et al, 2004; Lemon and Griffiths, 2005; Seo and Jang, 2013). Recent development of diffusion tensor tractography (DTT) allows three-dimensional reconstruction of neural tract in brain in vivo .…”