The origin of large neurons of the substantia nigra, ventral tegmental area of Tsai and interpeduncular nucleus was determined in three-weekold rats receiving a single injection of thymidine-H" during gestation. These neurons underwent final mitotic division on embryonic days 11 through 15 with maximal production on days 1 4 and 15. Glia and the smallest type of granular neurons were produced from day 11 through 22. Cells in the ventral angle of the neuroepithelium were not labeled one hour after injection of thymidine-H3 in any of the series.Study of animals receiving a single injection of thymidine-H3 during gestation and killed at serial intervals thereafter showed that neurons forming the substantia nigra migrated from the middle third of the basal neuroepithelium and moved between existing cells in radial patterns. Production of neurons specifically for each division of the substantia nigra was not observed either in crosssection or rostrocaudally, nor was the destination of neurons related to their time of origin. The ventral tegmental area of Tsai and interpeduncular nucleus formed from neurons originating in the medial third of the basal plate and migrating almost to the ventral surface of the mesencephalon. The neurons then divided into two streams to create a pattern of an inverted fountain comparable to the distribution of neurons containing catecholamines. Some of these neurons may have contributed to the substantia nigra. The primordia in all three nuclear areas were first seen on embryonic day 18.

Early stages in chick neurogenesis were investigated with tritiated thymidine (3H-Tdr) autoradioraphy to determine the location and identity of the first neurons produced for the central nervous system. These cells have been shown to arise prior to neural tube closure (Sechrist, '75). Chicks were treated at selected intervals between 20 and 72 hours of incubation with 3H-Tdr in a modified pulse-labeling technique, and terminated on the 18th day of embryonic development (E18), when neuronal types could be determined. Some of the earliest neurons start their final DNA synthesis before 20 hours of incubation (head process, Hamburger-Hamilton stage 5). These are primarily medium-sized cells of the reticular formation in the medulla and at the diencephalic-mesencephalic junction, but also in the intermediate zone of the spinal cord. Motor neurons of the brainstem and spinal cord begin to appear next, after 26-28 hours incubation; the first sensory neurons arise after 32 hours. Other workers (Ramon y Cajal, '60; Tello, '23; Windle and Austin, '36) found that neurons of the reticular formation were the first to differentiate neurofibrils, during the latter part of E2, indicating that fibrillogenesis in these cells begin about 24 hours after the initial cessation of DNA replication.

with tritiated origin and 2)School, Houston, Texas 77025Early neurogenesis was studied in two series of mouse embryos thymidine ("H-Tdr) autoradiography to determine 1) the time of the identity of the first postmitotic neurons. Time of origin was studied in embryos cumulatively labeled on the 9th-11th day of gestation (E8, E9, or E10, since the day of finding the vaginal plug is EO) and terminated after one cell cycle (8 hours). Autoradiographs were examined for unlabeled neurons, those which had undergone final DNA synthesis and which were usually also postmitotic. A 16-somite embryo, cumulatively labeled from the 6-somite stage, demonstrated 234 such cells in both alar and basal plates from the caudal diencephalon to the cervical spinal cord. Some of these young neurons, therefore, arose prior to neural tube closure, which begins a t the 7-somite stage. Data from other embryos in this series suggests that the first neurons arise at the 1-2 somite stage.Early arising neurons were identified in embryos pulse labeled with :3H-Tdr during E8-11 and killed after postnatal day (P) 30, when neuronal types could be determined. Autoradiographs were examined for heavily labeled cells, those in final DNA synthesis at the time of treatment. Heavily labeled cells in the youngest mouse in this series (injected a t E8%; ca. 8-somite stage) were primarily small-to medium-sized neurons of the brainstem reticular formation, but also some small neurons of the superior olivary nucleus and large primary sensory neurons of the mesencephalic nucleus of the trigeminal nerve. The earliest neurons in the spinal cord appeared early on E9, were medium sized, and were located in the ventral horn and the intermediate zone.Comparisons between the results of this study and those of McConnell and Sechrist ('80) in the chick suggest that the youngest stages of neurogenesis are similar. The first chick nerve cells arise just before formation ofthe first somites; a slightly later time is indicated in the mouse. Reticular neurons are the earliestarising cells in the chick and make up the majority of the population in each of the youngest chick and mouse stages obtained. Motor and sensory neurons do not begin to originate in large numbers until later, during E3 in the chick and E9 in the mouse.The historical background of early vertebrate neurogenesis has been described in an earlier publication on the chick (see McConnell and Sechrist, '80). In that work, the early arising medullary neurons which were seen in the chick by Sechrist ('75) were identified as small and medium-sized cells of the reticular formation. Earlier, Windle ('44) had suggested that differences in behavioral development could be accounted for by distinct species differences in neuroanatomical development, with integrator neurons appearing first in birds and reptiles, and motor neurons first in mammals. The current study was undertaken to determine if neurons similar to those in the chick could be found in a representative mammal, the mouse, and whether the sequence of o...

Midbrains of ten young adult rats were sectioned serially in three planes to study the detailed cytoarchitecture of the substantia nigra. These neurons measure 8 to 17 p in diameter. In comparison, the largest neurons in the midbrain measure 20 to 40 SL; hence, neurons are designated according to size as follows: those measuring 18 to 40 CL, large; 12 to 17 SL, medium; and 8 to 11 CL, small. The substantia nigra of the rat contains non-pigmented neurons in three divisions: pars reticulata, pars compacta, and pars lateralis. The pars reticulata is the largest division and has the longest rostrocaudal extent. It contains neurons of small size medially and of medium size laterally. This finding correlates with described differences in connections. Three-dimensionally, the pars reticulata is an oblate spheroid with the long axis in the rostrocaudal plane. The pars compacts is a triangular layer dorsal to reticulata. It is subdivided into rostral and caudal portions at the level of the fibers of the basal optic root. Neurons in both subdivisions are medium in size, but cells rostrally are darker than those caudally. The pars lateralis is a column of neurons with its long axis located in the rostrocaudal plane. It lies dorsolateral to the pars reticulata and the pars compacts, with occasional connections to both by cellular strands. The pars lateralis has rostral and caudal portions; neurons rostrally are medium in size and round; caudally, however, neurons are variable in size, dark, stellate or fusiform, and have long processes.The substantia nigra of mammals, including the rat, has been studied by previous investigators who examined the cytoarchitecture of the midbrain or brain stem (Huber et al., '43; Rioch, '29; Taber, '61), but we could not find a report of a cytoarchitectural study limited to this nucleus in lower animals. The substantia nigra in man has been described in detail by Hassler ('37), and to a lesser extent by Olszewski and Baxter ('54). The rat is used so frequently in experimental work, especially in behavioral studies, that a detailed account of the different types of neurons would be useful. In addition, recent studies on the connections of the substantia nigra to other parts of the brain have revealed considerable specificity. The objective of the present study was to provide more detailed information on the topography, morphology and cytoarchitecture of the substantia nigra of the rat than is presently available. AM. J. ANAT., 129: 417438. MATERIALS AND METHODSTen young adult female Charles River derived (CD) rats were used. Their body weights ranged from 280 to 328 gm and the brains from 1.85 to 2.10 gm. The rats were anesthetized with ether and decapitated. The brains were fixed in 10% formalin for at least seven days. Each brain was placed on its ventral surface, and cut dorsoventrally to remove the forebrain anteriorly and the brain stem caudal to the pons. The anterior cut surface was in the coronal plane. Horizontal sections were made by cutting brains parallel to the dorsal surf...