To investigate the role of 5-HT in the development of the somatosensory cortex, this amine was depleted in newborn (P-0) rats with a single subcutaneous injection of the toxin 5,7-dihydroxytryptamine (5,7-DHT) and thalamocortical organization was assayed by application of the carbocyanine dye Di-I to the thalamocortical radiations or ventrobasal thalamus, or by staining cortical sections for AChE or cytochrome oxidase (CO). High-performance liquid chromatographic analysis of cortices from animals killed on P-6 or P > 60 demonstrated that 5,7-DHT treatment resulted in 85.04 +/- 12.6% and 72.5 +/- 1.5% reductions in cortical 5-HT, respectively. Alternate cortices from the brains of animals killed on P-6 processed for 5-HT immunoreactivity demonstrated a complete absence of the vibrissa-related pattern of immunoreactivity and only a small number of coarse immunoreactive axons. The 85% depletion of 5-HT did not alter the somatotopic organization of thalamocortical afferents in animals killed on P-6 or P > 60, but it did cause 30.5 +/- 7.3% and 19.1 +/- 3.7% reductions in the cross-sectional areas of the patches of thalamocortical afferents corresponding to the long mystacial vibrissae (p < 0.05). These reductions were not associated with significant reductions in either brain or cortical weight or with decreases in the dimensions of the thalamic representation of the vibrissa follicles. These results indicate that 5-HT plays a significant role in the development of the thalamic innervation of the primary somatosensory cortex.

Retrograde tracing with true blue (TB) and diamidino yellow (DY) and anterograde tracing with either wheatgerm agglutinin-conjugated horseradish peroxidase (WGA-HRP) or Phaseolus vulgaris leucoagglutinin (PHA-L) were employed to investigate the projections from trigeminal nucleus principalis (PrV) and trigeminal subnucleus interpolaris (SpI) to their targets in the medial ventral posterior (VPM) and posterior (POm) nuclei of the thalamus. Many more cells in both PrV and SpI were labeled by tracer injections into VPM than into POm. Only a very small number of double-labeled neurons were observed in either PrV or SpI. However, a significantly higher percentage of SpI cells projected to POm or to both POm and VPM than was the case for PrV. Anterograde tracing with WGA-HRP showed that the projections from both PrV and SpI to VPM were much denser than those from the same nuclei to POm. Small injections of PHA-L into either PrV or SpI produced a focus of fairly dense labeling in VPM and much more diffuse terminal labeling in POm. These anatomical data provide evidence for two separate trigeminothalamic pathways, one originating from PrV and the second originating from SpI. Both of these pathways converge and diverge at the thalamic level. That is, information from the PrV pathway and from the SpI pathway are both provided to VPM in a morphologically restricted fashion and to POm in a morphologically widespread fashion.

Anterograde and retrograde tracing with biotinylated dextran amine and Phaseolus vulgaris leukoagglutinin was used to assess projection patterns within the vibrissae representation of the rat's primary somatosensory cortex (S-I). Large and small injections of either tracer into the center of the vibrissae representation yielded dense anterograde and retrograde labelling throughout much of the tangential extent of the vibrissae representation within S-I. In all layers, the pattern and extent of retrograde and anterograde label was in rough congruence. The organization of this labelling varied across cortical layers. In layers II and III, labelled fibers extended away from injection sites in all directions and yielded a uniform pattern, which decreased in density with increasing distance from the tracer injection. There was a tendency for labelling to be more extensive along the representation of the row of vibrissae follicles that included the injection site than across rows. There was also a tendency for anterograde labelling to be more extensive in the direction of the representation of follicles more rostral on the face than that injected. In lamina IV, both labelled fibers and cells were restricted for the most part to the septa regions between the barrels. However, a small number of retrogradely labelled neurons were also located in the barrels (approximately one-ninth of the number found in the septa). The pattern observed in laminae II-III was repeated in layers V and VI. In these laminae, there was no evidence of a pattern of intracortical connections related to the vibrissae representation in overlying lamina IV.

Immunocytochemistry with an antiserum directed against serotonin (5-HT) was used to assess the development of the representation of the body surface in the rat's primary somatosensory cortex (S-I). Within 1 hour of birth (P-O), 5-HT-positive fibers were present in the marginal zone, the cortical plate, and developing layers V and VI. Immunoreactivity in the marginal zone consisted of a thin band of coarse fibers oriented parallel to the pia. Only a small number of isolated fibers were visible in the cortical plate. A denser network of both coarse and fine fibers could be seen in presumptive layers V and VI. By the first hour of P-I, 5-HT-positive axons in the deeper cortical plate were organized into a crude representation of the rat's body surface. At this age, aggregates of fibers corresponding to the head, lower jaw, trunk, and forepaw could be clearly distinguished. These regions of dense 5-HT immunoreactivity consisted primarily of fine caliber axons that had invaded the lower part of the cortical plate. Dense aggregates of fine caliber axons were also visible in developing layers V and VI. Coarse 5-HT-positive fibers were visible in all layers, but they did not appear to contribute to the pattern that corresponded to the body surface. By the first hour of P-2, the map of the body surface in S-I was more refined and a row-related organization of 5-HT-immunoreactive fibers was visible in the portion of the cortex representing the vibrissa pad. The laminar distributions of coarse and fine caliber serotoninergic axons at this age were essentially the same as on P-I. By P-2.5 (60 hours after birth), patches of 5-HT-positive fibers corresponding to individual vibrissa follicles were clearly evident. These consisted of dense aggregates of fine caliber axons that were centered in presumptive layer IV, but which also extended above and below this lamina. Over the next 3 days, the pattern continued to mature. By P-4, dense 5-HT labelling was also visible in the secondary somatosensory cortex (S-II). By the beginning of P-5, clusters of fibers corresponding to more rostral facial hairs and individual digits within the forepaw representation could also be discerned. By P-12, the differential distribution of 5-HT fibers in S-I was no longer visible. Thus, immunocytochemistry for serotonin showed a representation in S-I homeomorphic with the body surface prior to the age at which it can be discerned with other methods thought to reveal thalamocortical axons. Transection of the infraorbital nerve (ION) on the day of birth altered the organization of the vibrissal representation in the contralateral cortex from the earliest age at which it could be detected by 5-HT immunocytochemistry in normal animals. However, the departure from the normal organization was gradual. Row-related organization was clearly visible in the cortices of rats sacrificed on P-3, but not in those of rats that were killed on P-5. These results suggested that the organization of the 5-HT innervation of the cortex may be guided by thalamic afferents an...

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Serotonin (5-HT)-immunoreactive axons are densely distributed in the primary visual and somatosensory cortices of rats, mice, and hamsters for the first 2 weeks of life, and a recent study from this laboratory has demonstrated that 5-HTIB receptors assume a pattern that exactly matches that of the serotoninergic axons. The differential distribution of these receptors is also transient. In the present study, we combined receptor binding autoradiography with neurochemical ablation of5-HT axons or electrolytic lesions of the dorsal thalamus in an effort to determine the neural elements upon which the 5-HTIB receptors were located. Subcutaneous iD'ections of the toxin 5,7-dihydroxytryptamine, made on the day of birth, totally eliminated the dense and patterned 5-HT innervation of the somatosensory and striate cortices of rats killed on postnatal day 8 but had no qualitative effect upon the distribution or density of 5-HTIB receptors in either of these cortical regions in animals killed at the same age. Conversely, electrolytic lesions of the dorsal thalamus made on postnatal day 6 resulted in a complete loss of the dense and patterned distribution of 5-HTIB receptors in rats killed on postnatal day 8. These results indicate that thalamocortical axons transiently express 5-fiT1B receptors.Thalamic axons and lamina IV neurons in the cortex of perinatal rodents are arrayed in clusters that correspond to the body surface (1-3). The development of this precise, anatomically demonstrable somatotopic representation depends upon peripheral information (4) that is almost certainly conveyed to the cortex by thalamocortical fibers. For about the first 2 weeks of life, the serotoninergic innervation of the cerebral cortex has a distribution closely matching that of the somatosensory and visual thalamocortical afferents (5-8) and there is recent evidence that depletion of serotonin (5-HT) from the developing somatosensory cortex may delay the maturation of the somatotopic pattern of thalamocortical afferents and lamina IV neurons (9, 10).We do not know the mechanisms by which 5-HT might influence the development of either thalamocortical axons or cortical cells. One approach toward answering this question is determining the types and locations of the 5-HT receptors in the cortex during development. A recent study from this laboratory has demonstrated that one class of 5-HT receptors, 5-HT1B, is transiently arrayed in the somatosensory and visual cortices in a way that closely matches the distribution of specific thalamic afferents and the transient 5-HT innervation of these cortical fields (11). In the adult brain, 5-HT1B receptors have been shown to be autoreceptors that regulate 5-HT release from serotoninergic axons (12, 13) and heteroreceptors that are likely to be located on retinal axons, spinal primary afferents, and other non-5-HT axons (14-16). These results raised the possibility that the 5-HT1B receptors (right hemisphere) Thalamotomy on P-6 P-8 3 Autoradiography P-, postnatal day; 5,7-DHT, 5,7-dihydroxytrypta...

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