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S A Bayer

Publications and source records attributed to S A Bayer.

At least 55 records · Page 3Linked to original sources

Development of the precerebellar nuclei in the rat: III. The posterior precerebellar extramural migratory stream and the lateral reticular and external cuneate nuclei.

Sequential thymidine radiograms from rats injected on day E15 and killed thereafter at daily intervals up to day E22 were analyzed to trace the migratory routes and settling patterns of neurons of the lateral reticular nucleus and the external cuneate nucleus. The neurons of the lateral reticular and external cuneate nuclei originate in the primary precerebellar neuroepithelium at the same site as the inferior olivary neurons but follow a different migratory route. The labeled young neurons that are produced on day E15 (the last one-third of the total) join the posterior precerebellar extramural migratory stream. The cells move circumferentially over the wall of the medulla in a ventral direction and by day E17 reach the midline and cross it beneath the inferior olive. The crossing cells apparently continue to migrate circumferentially on the opposite side. One complement of these cells begins to form a ventrolateral extramural condensation on day E19. By day E20 some cells begin to penetrate the parenchyma and settle as neurons of the lateral reticular nucleus. The settling of the lateral reticular neurons continues on the following day, and by day E22 all the cells destined for the lateral reticular nucleus have penetrated the parenchyma. A dorsomedial-to-ventrolateral neurogenetic gradient is indicated for the settling lateral reticular neurons. Another complement of migrating cells continues dorsally and forms a condensation on day E19 that we interpret as the external cuneate component of the crossed stream. These cells begin to penetrate the parenchyma on day E20, and by days E21 and E22 two components of the external cuneate nucleus are identifiable-the dorsal and ventral external cuneate nuclei. The neurons of the lateral reticular and external cuneate nuclei differ from neurons of all the other precerebellar nuclei in that their cerebellar projection is predominantly ipsilateral. We speculate that the axons of all precerebellar neurons are genetically specified to cross the midline ventrally to provide a contralateral efferent projection, but this is modified in the case of the ipsilaterally projecting lateral reticular and external cuneate neurons by the cell bodies following their neurites to the opposite side.

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Development of the precerebellar nuclei in the rat: IV. The anterior precerebellar extramural migratory stream and the nucleus reticularis tegmenti pontis and the basal pontine gray.

Sequential thymidine radiograms from rats injected on days E16, E17, E18, and E19 and killed 2 hours after injection and at daily intervals up to day E22 were used to establish the site of origin, migratory route, and settling patterns of neurons of the nucleus reticularis tegmenti pontis and basal pontine gray. The nucleus reticularis tegmenti pontis neurons, which are produced predominantly on days E15 and E16, derive from the primary precerebellar neuroepithelium. These cells, unlike those of the lateral reticular and external cuneate nuclei, take an anteroventral subpial route, forming the anterior precerebellar extramural migratory stream. This migratory stream reaches the anterior pole of the pons by day E18. In rats injected on day E16 and killed on day E18 some of the cells that reach the pons are unlabeled, indicating that they represent the early component of neurons generated on day E15. The cells labeled on day E16 begin to settle in the pons on day E19, 3 days after their production. These cells, migrating in an orderly temporal sequence, form a posterodorsal-to-anteroventral gradient in the nucleus reticularis tegmenti pontis. Unlike the neurons of all the other precerebellar nuclei, the basal pontine gray neurons derive from the secondary precerebellar neuroepithelium. The secondary precerebellar neuroepithelium forms on day E16 as an outgrowth of the primary precerebellar neuroepithelium, and it remains mitotically active through day E19, spanning the entire period of basal pontine gray neurogenesis. The secondary precerebellar neuroepithelium is surrounded by a horizontal layer of postmitotic cells, representing the head-waters of the anterior precerebellar extramural migratory stream. In rats injected on day E18 and killed on day E19 the cells are labeled in the proximal half of the stream around the medulla but those closer to the pons are unlabeled, indicating an orderly sequence of migration. In rats injected on day E18 and killed on day E20 the labeled cells reach the pole of the pons. In the basal pontine gray the sequentially generated neurons settle in a precise order. The neurons generated on day E16 form a small core posteriorly and the neurons generated on days E17, E18, and E19 form regular concentric rings around the core in an inside-out sequence.

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Neurogenesis in subnuclei of the rat interpeduncular nucleus and medial habenula.

Development of the rat habenulo-interpeduncular system is of interest because of its highly ordered adult structure, including seven subnuclei within the interpeduncular nucleus (IPN), localization of synapses of different types and medial habenular (MH) sites of origin within the subnuclei, and differential localization of neurochemicals amongst the subnuclei. In order to further investigate the mechanisms by which these features are produced, the birthdays of neurons within IPN and MH were investigated. All IPN neurons were formed on embryonic days (E) 12 to 16. Birthdays varied for the subnuclei of IPN with the earliest being the serotonin containing apical subnucleus (p less than 0.0001) and the latest being the rostral subnucleus (p less than 0.0001). Rostral lateral and lateral subnuclei were approximately simultaneous with apical, and the intermediate and central subnuclei, related to each other in a number of other ways, had simultaneous birthdays earlier than the rostral subnucleus (p less than 0.0001) and later than the other subnuclei (p less than 0.0001). The medial habenula was found to consist of three regions, termed medial, lateral and dorsal, whose neurons undergo their final mitoses on E15-16, 16-17 and 17-18, respectively. These findings provide additional support for the validity of IPN subnuclei as currently delineated. They suggest mechanisms of development which involve early interactions between specific groups of MH neurons and specific groups of IPN neurons. It is proposed that a sequence of several control mechanisms operates during development to produce this complex system.

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Neurogenesis in the anterior olfactory nucleus and its associated transition areas in the rat brain.

Neurogenesis in the rat olfactory peduncle was examined with [3H]thymidine autoradiography. Animals in the prenatal groups were the offspring of pregnant females given an injection of [3H]thymidine on two consecutive gestation days. Nine groups of embryos were exposed to [3H]thymidine on embryonic days (E) E13-E14, E14-E15,...E21-E22, respectively. One group of postnatal animals was given four consecutive injections of [3H]thymidine on postnatal days (P) P0-P3. On P60, the percentage of labeled cells and the proportion of cells originating during either 24 or 48 hr periods were quantified at seven anatomical levels through both the anterior olfactory nucleus and the transition areas. A caudal (older) to rostral (younger) neurogenetic gradient is found both within and between structures in the olfactory peduncle. Neurons in the dorsal, lateral, and ventral-lateral transition areas are generated mainly between E14 and E19, those in the anterior olfactory nucleus mainly between E15 and E21. Only 3-4% of the neurons in the most anterior pars lateralis and pars dorsalis originate after birth. All parts of the anterior olfactory nucleus show a strong superficial (older) to deep (younger) neurogenetic gradient (the 'outside-in' pattern). In contrast, neurons in the ventral-lateral transition area and in the dorsal transition area originate in a deep to superficial neurogenetic gradient (the 'inside-out' pattern), suggesting that these areas are, in reality, primary olfactory cortex. The lateral transition area is truly 'transitional', showing no neurogenetic gradient along the superficial-deep plane. The medial transition area originates between E15 and E19 in a center (older) to edge (younger) 'sandwich' neurogenetic gradient along the rostrocaudal plane, a pattern apparently unrelated to neurogenetic gradients in other olfactory peduncle structures. These data suggest that characteristic patterns of neurogenesis, namely the 'inside-out' vs the 'outside-in' gradients, permit the assignment of different structures to cortical vs ganglionic cytoarchitectonic components of the olfactory relay system.

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Neurogenesis in the rat primary olfactory cortex.

Neurogenesis in the rat primary olfactory cortex was examined with [3H]thymidine autoradiography. The experimental animals were the offspring of pregnant females given an injection of [3H]thymidine on two consecutive gestation days. Nine groups of embryos were exposed to [3H]thymidine on E13-E14, E14-E15....E21-E22, respectively. On P60, the percentage of labeled cells and the proportion of cells originating during 24 hr periods were quantified at selected anatomical levels of the anterior and posterior piriform cortex, dorsal lateral peduncular cortex, and posterior two-thirds of the ventral agranular insular cortex. Throughout most of the primary olfactory cortex, deep cells are generated earlier than superficial cells: the 'inside-out' pattern. Neurons in the anterior (prepiriform) cortex are located lateral to the caudal anterior olfactory nucleus and olfactory tubercle, and are generated mainly between E14 and E18 in a caudal (older) to rostral (younger) neurogenetic gradient. Neurons in the posterior (periamygdaloid) cortex are located lateral to the caudal olfactory tubercle and amygdala, and are generated mainly between E14 and E17 simultaneously along the rostrocaudal plane. Superficial cells in the piriform cortex have some additional neurogenetic gradients; ventromedial cells forming transition zones with either the olfactory tubercle or amygdala originate earlier than cells located dorsally and laterally. In the posterior piriform cortex, younger neurons are located at middle dorsoventral levels while older neurons lie above and below. Neurons in the dorsolateral peduncular cortex originate between E14 and E20 in a caudal to rostral gradient of neurogenesis; caudal parts also have a lateral to medial neurogenetic gradient. The most lateral part of the dorsolateral peduncular cortex is unique and does not have the typical 'inside-out' cortical neurogenetic gradient. Neurons in the ventral agranular insular cortex (area 13) originate mainly between E15 and E17 in combined caudal to rostral and ventral to dorsal neurogenetic gradients. The neurogenetic gradients in the primary olfactory cortex, along with patterns of neurogenesis throughout the olfactory projection field are related to the termination patterns of afferents from the main olfactory bulb.

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Embryonic development of the rat cerebellum. I. Delineation of the cerebellar primordium and early cell movements.

Short-survival and long-survival thymidine radiograms, and methacrylate-embedded tissue from normal and X-irradiated rat embryos were used to delineate the neuroepithelial source of the cerebellum and trace the earliest cell movements. The cerebellar anlage, crescent shaped, is demarcated by two ventricular landmarks, the anterior extension of the tela choroidea of the fourth ventricle and the embryonic cerebellar fissure. The cerebellar tela choroidea extends from the medullary fourth ventricle posteromedially to the lateral recess of the pontine fourth ventricle anterolaterally. The embryonic cerebellar fissure begins caudally as a single midline incision beneath the fused posterior cerebellar primordium, then splits to follow the unfused cerebellar halves, first separating each from the isthmus then from the pons. The cerebellar primordium is divided into three parts. The lateral cerebellar primordium caps the lateral recess of the fourth ventricle; it is contiguous with the pons medially and separated ventrally from the anlage of the cochlear nuclei by the tela choroidea. The subisthmal cerebellar primordium is situated beneath the isthmus, medially lining the isthmus canal. Laterally and posteriorly, it is continuous with the lateral and postisthmal primordia. The postisthmal cerebellar primordium caps the postisthmal recess of the fourth ventricle and extends to the medullary fourth ventricle. As we shall describe later, each of these primordia is a source of different components of the developing cerebellum. Most cells of the superficially located nuclear transitory zone are labeled with 3H-thymidine administered on day E14 but not thereafter. A high proportion of the cells of the deeper cortical transitory zone could still be labeled on day E15. This supports the assumption made earlier that the first is composed of differentiating deep neurons, the second of Purkinje cells. The cells of the nuclear transitory zone originate in the lateral cerebellar primordium near the junction with the tela choroidea prior to the formation of the germinal trigone and migrate in a superficial position medially. Beginning on day E16, the nuclear transitory zone splits into two components. One has transversely oriented cells that seem to be the source of a decussating fiber tract, presumably the hook bundle of Russell. The other is composed of longitudinally oriented cells that apparently contribute fibers to the ipsilateral superior cerebellar peduncle. The translocation of the cells of the nuclear transitory zone from the cerebellar surface to its depth, to form the deep nuclei, and the radial migration of the cells of the cortical transitory zone to the surfa

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Embryonic development of the rat cerebellum. II. Translocation and regional distribution of the deep neurons.

In thymidine radiograms and plastic-embedded sections, the migration of cerebellar deep neurons was traced from their germinal source to their final settling sites. The route proved to be roundabout and three developmental events could be distinguished during the process. First, between days E14 and E16, transversely oriented cells of the nuclear transitory zone move in an arc from the ventrolateral neuroepithelium of the lateral cerebellar primordium in a medial direction. Second, between days E16 and E18, the cells of the rostral component of the nuclear transitory zone assume a longitudinal orientation. We postulated that this is the period of axonogenesis, the longitudinally oriented cells issuing efferents that join the superior cerebellar peduncle ipsilaterally and the transversely oriented cells (representing the neurons of the caudal fastigial nucleus) sending decussating fibers to the uncinate fasciculus (the hook bundle of Russell). Third, between days E18 and E21, the earlier-produced superficial cells of the nuclear transitory zone and the later-produced deep cells of the cortical transitory zone (the young Purkinje cells) exchange positions. The descent of the deep neurons is in the direction of the fibers of the inferior cerebellar peduncle, which becomes distributed throughout the cerebellum on day E17. The ascent of the Purkinje cells is in the direction of the external germinal layer, which begins to spread from caudal to rostral on day E17. The three deep nuclei, the lateral (dentate), interpositus, and medial (fastigial), can be distinguished before their descent into the depth of the cerebellum, and by day E22 a small-celled and a large-celled subdivision is identifiable in each nucleus.

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Embryonic development of the rat cerebellum. III. Regional differences in the time of origin, migration, and settling of Purkinje cells.

The time of origin, site of origin, migratory path and settling pattern of the Purkinje cells of the cerebellar hemispheres, anterior vermis, and posterior vermis were investigated in thymidine radiograms and plastic-embedded materials from rat embryos ranging in age from 15 to 22 days. In the hemispheres there is a rostral-to-caudal cytogenetic gradient: the Purkinje cells of lobulus simplex, crus I, and crus II are produced earlier than the Purkinje cells of the paramedian lobule and paraflocculus, followed by the Purkinje cells of the flocculus. The Purkinje cells of the vermis, in general, are generated later than those of the hemispheres, and with a reverse gradient from caudal to rostral: the Purkinje cells of the posterior vermis (lobules X-VI) being produced ahead of the Purkinje cells of the anterior posteriorly directed wedge of early-produced Purkinje cells through the vermis. Evidence was obtained that the Purkinje cells of the hemispheres derive from the lateral cerebellar primordium capping the lateral recess of the fourth ventricle anteriorly. The Purkinje cells of the anterior vermis originate from the subisthmal cerebellar primordium medially lining the isthmal canal. The Purkinje cells of the posterior vermis originate in the postisthmal cerebellar primordium overlying the tela choroidea caudally. The young Purkinje cells migrate from the neuroepithelium to the surface of the cerebellum in a strictly caudal-to-rostral order, paralleling the spread of the EGL superficially from posteroventral to anterodorsal. This pattern is independent of the time of origin of Purkinje cells. In the posterior vermis the earliest-settling Purkinje cells of the uvula follow a short radial course, and a discrete Purkinje layer is formed 3 days after they are generated. In the anterior vermis the Purkinje cells of lobulus centralis, which follow an anterodorsal migratory course, are still settling on day E22, 7 days after their production, presumably awaiting the fusion of the cerebellar base anteriorly. The fissura prima forms medially at the interface region of Purkinje cells derived from the postisthmal and subisthmal cerebellar primordia. For 1-2 days after their settling, the Purkinje cells of the newly forming lobules can be distinguished by certain cytological criteria from the Purkinje cells in the more caudally-situated, earlier-settled lobules.

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3H-thymidine-radiographic studies of neurogenesis in the rat olfactory bulb.

Neurogenesis in the rat olfactory bulb was examined with 3H-thymidine-radiography. For the animals in the prenatal groups, the initial 3H-thymidine exposures were separated by 24 h; they were the offspring of pregnant females given two injections on consecutive embryonic (E) days (E12-E13, E13-E14, . . . E21-E22). For the animals in the postnatal (P) groups, the initial 3H-thymidine injections were separated by 48 h, each group receiving either four (PO-P3, P2-P4, . . . P6-P9) or two (P8-P9, P10-P11, . . . P20-P21) consecutive daily injections. On P60, the percentage of labeled cells and the proportion of cells added during either 24 h or 48 h periods were quantified at several anatomical levels for each neuronal population in the main olfactory bulb (mitral cells, tufted cells, granule cells, interneurons in the external plexiform layer, periglomerular granule cells) and accessory olfactory bulb (output neurons, granule cells, periglomerular granule cells). The total time span of neurogenesis extends from E12 to beyond P20. Output neurons are prenatally generated over 5-9 day periods (with most neurogenesis occurring over 2-4 days) in a strict sequential order beginning with the accessory bulb output neurons (E13-E14) and ending with the interstitial tufted cells lying between the glomeruli in the main bulb (E20-E22). These data are correlated with the main and accessory bulb projection fields in the amygdala and with the chronology of amygdala neurogenesis. With the exception of the granule cells in the accessory bulb (88% generated between E15-E22), the rest of the interneuronal populations are generated postnatally and nearly simultaneously. While most neurons (75-80%) originate during the first three weeks of life, all interneuronal populations, including accessory bulb granule cells, show some neurogenesis beyond P20. Injections of 3H-thymidine in juvenile and adult rats indicates neurogenesis up to P60 in the accessory bulb and up to P180 in the main bulb, especially in the main bulb granule cell population. There is circumstantial evidence for turnover of main bulb granule cells during adult life.

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Changes in the total number of dentate granule cells in juvenile and adult rats: a correlated volumetric and 3H-thymidine autoradiographic study.

The total number of granule cells in the dentate gyrus was estimated in 17 male rats, four each aged 30, 120, and 200 days, and five aged 365 days. There is a substantial 35-43% linear increase between 1 month and 1 year. Two parameters of the granular layer are involved in the numerical change. First, total granular layer volume grows linearly with age. Second, average volume of a single granule cell nucleus in the ventral dentate gyrus decreases with age. Older rats tend to have a larger granular layer filled with more and smaller cells. In another group of 21 male rats, 3H-thymidine injections were given on four consecutive days during juvenile (30-33, n = 6) and adult life (60-63, n = 5; 120-123, n = 6; 180-183, n = 4). All animals survived to 200 days of age. The proportion of labeled mature granule cells and labeled presumptive granule cell precursors were determined in anatomically-matched slices. With older ages at injection, there is a decline in labeled mature granule cells and a concurrent increase in labeled precursors. These data are compatible with the constant level of granule cell increase determined volumetrically. Most of the late granule cells originate nearly simultaneously along the base of the main bulk of the granular layer; very few are found in the dorsal tip (septal extreme) and ventral tip (temporal extreme). This study is the first demonstration of a net numerical gain in a neuronal population during adulthood in the mammalian brain. Since the granule adulthood in the mammalian brain. Since the granule cells play a pivotal role in hippocampal function, these data suggest that their influence grows with age.

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Development of the brain stem in the rat. V. Thymidine-radiographic study of the time of origin of neurons in the midbrain tegmentum.

Groups of pregnant rats were injected with two successive daily doses of 3H-thymidine from gestational day E12 and 13 (E12 j3) until the day before parturition (E21 k2) in order to label in their embryos the proliferating precursors of neurons. At 60 days of age the proportion of neurons generated (no longer labeled) on specific embryonic days was determined quantitatively in 18 regions of the midbrain tegmentum. The neurons of the oculomotor and trochlear nuclei are generated concurrently on days E12 and 13. There was a mirror image cytogenetic gradient in these nuclei and this was interpreted as the dispersal of neurons derived from a common neuroepithelial source to the medial longitudinal fasciculus. Neurons in three other components of the tegmental visual system are produced in rapid succession after the motor nuclei. In the nucleus of Darkschewitsch peak production time was on day E12 and 13, extending to day E15; in the Edinger-Westphal nucleus the time span was the same but with a pronounced between days E13; finally, the neurons of the parabigeminal nucleus were produced between days E13 and E15 with a peak on day E14. The neurons of the periaqueductal gray were generated between days E13 and 17 with a pronounced ventral-to-lateral and lateral-to-dorsal gradient. In the red nucleus the neurons were produced on days E13 and E14 with a caudal-to-rostral gradient: the cells of the magnocellular division preceding slightly but significantly the cells of the parvocellular division. The neurons of the interpeduncular nucleus originated between days E13 and E15; the peak in its ventral portion was on day E13, in its dorsal portion on days E14 and E15. A ventral-to-dorsal gradient was seen also in both the dorsal and the median raphe nuclei in which neuron production occurred between days E13 and E15. The neurons of the pars compacta and pars reticulate of the substantia nigra were both produced between days E13 and E15 with a modified lateral-to-medial gradient. This gradient extended to the ventral tegmental area where neurons of the pars medialis were produced between days E14 and E16. With the exception of the central gray, neuron production was rapid and relatively early in the structures situated ventral to the midbrain tectum. A comparison of the cytogenetic gradients in the raphe nuclei of the lower and upper medulla, the pontine region, and the midbrain suggests that they originate from at least three separate neuroepithelial sources.

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Time of origin of neurons of the rat inferior colliculus and the relations between cytogenesis and tonotopic order in the auditory pathway.

Groups of pregnant rats were injected with two successive daily doses of 3H-thymidine from gestational day 12 and 13 (E12+13) until the day before parturition (E21+22) in order to label in their embryos the proliferating precursors of neurons. At 60 days of age the proportion of neurons generated (or no longer labelled) on specific embryonic days was determined quantitatively in six vertical strips of the inferior colliculus. It was established that the neurons of the inferior colliculus are produced between days E14 and the perinatal period in an orderly sequence: the earliest generated cells are situated rostrally, laterally and ventrally in the principal nucleus, the latest generated cells are situated caudally, medially and dorsally in the pericentral nucleus. This cytogenetic gradient suggested that the cells are produced dorsally in the caudal recess of the embryonic aqueduct and are deployed in an "outside-in" pattern. This study has brought to a conclusion our datings of neuron production in the central auditory pathway of the rat. The results revealed that in those structures in which a cytogenetic gradient could be recognized, the orientation of this gradient and the regional tonotopic order (demonstrated mostly in species other than the rat) tended to be aligned. Moreover, with the exception of the medial trapezoid nucleus and the dorsal nucleus of the lateral lemniscus (which receive contralateral input from the cochlear nuclei), sites with early-produced neurons correlated with units responding preferentially to high frequency tones and vice versa. This suggested that the orderly production of neurons within different components of the auditory system is a factor in their subsequent topographic organization. A comparison of the temporal order of neuron production in different components of the auditory pathway suggested that the establishment of orderly topographic relations between some of the structures (e.g., the medial geniculate body and the primary auditory cortex) takes place before this spatial relationship could be specified as a cochleotopic order.

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