Quantitative analysis of spinothalamic tract neurons in adult and developing mouse.

Understanding the development of nociceptive circuits is important for the proper treatment of pain and administration of anesthesia to prenatal, newborn, and infant organisms. The spinothalamic tract (STT) is an integral pathway in the transmission of nociceptive information to the brain, yet the stage of development when axons from cells in the spinal cord reach the thalamus is unknown. Therefore, the retrograde tracer Fluoro-Gold was used to characterize the STT at several stages of development in the mouse, a species in which the STT was previously unexamined. One-week-old, 2-day-old and embryonic-day-18 mice did not differ from adults in the number or distribution of retrogradely labeled STT neurons. Approximately 3,500 neurons were retrogradely labeled from one side of the thalamus in each age group. Eighty percent of the labeled cells were located on the side of the spinal cord contralateral to the injection site. Sixty-three percent of all labeled cells were located within the cervical cord, 18% in thoracic cord, and 19% in the lumbosacral spinal cord. Retrogradely labeled cells significantly increased in diameter over the first postnatal week. Arborizations and boutons within the ventrobasal complex of the thalamus were observed after the anterograde tracer biotinylated dextran amine was injected into the neonatal spinal cord. These data indicate that, whereas neurons of the STT continue to increase in size during the postnatal period, their axons reach the thalamus before birth and possess some of the morphological features required for functionality.

Asynchrony of the early maturation of white matter bundles in healthy infants: quantitative landmarks revealed noninvasively by diffusion tensor imaging.

Normal cognitive development in infants follows a well-known temporal sequence, which is assumed to be correlated with the structural maturation of underlying functional networks. Postmortem studies and, more recently, structural MR imaging studies have described qualitatively the heterogeneous spatiotemporal progression of white matter myelination. However, in vivo quantification of the maturation phases of fiber bundles is still lacking. We used noninvasive diffusion tensor MR imaging and tractography in twenty-three 1-4-month-old healthy infants to quantify the early maturation of the main cerebral fascicles. A specific maturation model, based on the respective roles of different maturational processes on the diffusion phenomena, was designed to highlight asynchronous maturation across bundles by evaluating the time-course of mean diffusivity and anisotropy changes over the considered developmental period. Using an original approach, a progression of maturation in four relative stages was determined in each tract by estimating the maturation state and speed, from the diffusion indices over the infants group compared with an adults group on one hand, and in each tract compared with the average over bundles on the other hand. Results were coherent with, and extended previous findings in 8 of 11 bundles, showing the anterior limb of the internal capsule and cingulum as the most immature, followed by the optic radiations, arcuate and inferior longitudinal fascicles, then the spinothalamic tract and fornix, and finally the corticospinal tract as the most mature bundle. Thus, this approach provides new quantitative landmarks for further noninvasive research on brain-behavior relationships during normal and abnormal development.

Assessment of the early organization and maturation of infants' cerebral white matter fiber bundles: a feasibility study using quantitative diffusion tensor imaging and tractography.

The human infant is particularly immature at birth and brain maturation, with the myelination of white matter fibers, is protracted until adulthood. Diffusion tensor imaging offers the possibility to describe non invasively the fascicles spatial organization at an early stage and to follow the cerebral maturation with quantitative parameters that might be correlated with behavioral development. Here, we assessed the feasibility to study the organization and maturation of major white matter bundles in eighteen 1- to 4-month-old healthy infants, using a specific acquisition protocol customized to the immature brain (with 15 orientations of the diffusion gradients and a 700 s mm(-2)b factor). We were able to track most of the main fascicles described at later ages despite the low anisotropy of the infant white matter, using the FACT algorithm. This mapping allows us to propose a new method of quantification based on reconstructed tracts, split between specific regions, which should be more sensitive to specific changes in a bundle than the conventional approach, based on regions-of-interest. We observed variations in fractional anisotropy and mean diffusivity over the considered developmental period in most bundles (corpus callosum, cerebellar peduncles, cortico-spinal tract, spino-thalamic tract, capsules, radiations, longitudinal and uncinate fascicles, cingulum). The results are in good agreement with the known stages of white matter maturation and myelination, and the proposed approach might provide important insights on brain development.

Loss of spinothalamic tract neurons following neonatal treatment of rats with the neurotoxin capsaicin.

The purpose of the present experiments was to determine whether the organization of spinothalamic tract (STT) cells of adult rats was altered following the loss of most of their small-diameter peripheral afferent fibers, resulting from the neonatal administration of capsaicin. Rat pups were randomly assigned to serve as normal controls, to serve as vehicle controls, or to receive subcutaneous injections of capsaicin (50 mg/kg) on postnatal day (PND) 1, 2, 7, or 15; or an injection on PND 1, 3, and 5. When 60 days old, they were anesthetized and received 0.1-microliter thalamic injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) in the area of the central lateral nucleus (CL), the posterior group (PO), and the ventrobasal complex (VB), or the area of CL or VB. Following a survival time of 48 hr, the animals were perfused, and neuronal HRP reaction product was visualized with tetramethylbenzidine. The number and distribution of WGA:HRP-labeled STT neurons varied in treated animals with the time of capsaicin injection. Rats injected with capsaicin on or before PND 7 demonstrated a significant reduction of labeled STT neurons from the superficial laminae of the spinal cord. Additionally, lamina I neurons were unlabeled in animals treated before PND 7 even with large thalamic injections. Differences in the distribution of labeled STT neurons could not be demonstrated for animals injected with capsaicin on PND 7 or PND 15, though there was a decrement in the number of labeled neurons in PND 7 animals. In order to make certain that absence of labeled STT neurons was not due to some technical error or to insufficient spread of WGA:HRP at the site of injection, six injections of WGA:HRP were placed in the thalamus of PND 1 and normal adult animals. Where the dense core of reaction product did not extend caudal to the posterior commissure, WGA:HRP-positive neurons were located and distributed similarly to those cases described for large thalamic injections. Neurons in superficial laminae of the nucleus proprius and lamina I of the contralateral spinal cord were labeled where the dense core of the thalamic injection extended into the mesencephalon of PND 1 animals. These studies indicate that the number and distribution of the cells of origin of the STT are altered in adult rats following their neonatal treatment with the neurotoxin capsaicin, and that this effect is limited to a critical postnatal period.