In the developing cerebellum, young granule neurons in the external germinal layer respond preferentially to BDNF, while mature neurons within the inner portion of the cerebellum respond preferentially to NT3. Here we show that this anatomic distinction reflects a developmentally regulated switch at the level of neurotrophin receptor gene expression. The salient feature of the developmental switch is a change in the ration of mRNA transcripts encoding functional BDNF and NT3 receptor tyrosine kinases. The ratio of the BDNF receptor trkB to the NT3 receptor trkC reverses from 5:1 in neonatal cerebellum to 1:3 in adult cerebellum. TrkB and TrkC are closely related transmembrane tyrosine protein kinases. However, activation of BDNF and NT3 receptors in cerebellar granule neurons do not give equivalent biological responses. In aggregate cell culture and single cell assays, BDNF enhances axonal outgrowth of early granule cells by influencing neurite elongation. In contrast, NT3 alters the morphology of outgrowth. Collectively, these findings suggest that regulation of neurotrophin receptors during cerebellar development is important for the timing and morphology of axonal growth. In the developing cerebellum, young granule neurons in the external germinal layer respond preferentially to BDNF, while mature neurons within the inner portion of the cerebellum respond preferentially to NT3. Here we show that this anatomic distinction reflects a developmentally regulated switch at the level of neurotrophin receptor gene expression. The salient feature of the developmental switch is a change in the ration of mRNA transcripts encoding functional BDNF and NT3 receptor tyrosine kinases. The ratio of the BDNF receptor trkB to the NT3 receptor trkC reverses from 5:1 in neonatal cerebellum to 1:3 in adult cerebellum. TrkB and TrkC are closely related transmembrane tyrosine protein kinases. However, activation of BDNF and NT3 receptors in cerebellar granule neurons do not give equivalent biological responses. In aggregate cell culture and single cell assays, BDNF enhances axonal outgrowth of early granule cells by influencing neurite elongation. In contrast, NT3 alters the morphology of outgrowth. Collectively, these findings suggest that regulation of neurotrophin receptors during cerebellar development is important for the timing and morphology of axonal growth. In the developing cerebellum, young granule neurons in the external germinal layer respond preferentially to BDNF, while mature neurons within the inner portion of the cerebellum respond preferentially to NT3. Here we show that this anatomic distinction reflects a developmentally regulated switch at the level of neurotrophin receptor gene expression. The salient feature of the developmental switch is a change in the ration of mRNA transcripts encoding functional BDNF and NT3 receptor tyrosine kinases. The ratio of the BDNF receptor trkB to the NT3 receptor trkC reverses from 5:1 in neonatal cerebellum to 1:3 in adult cerebellum. TrkB and TrkC are closely related transmembrane tyrosine protein kinases. However, activation of BDNF and NT3 receptors in cerebellar granule neurons do not give equivalent biological responses. In aggregate cell culture and single cell assays, BDNF enhances axonal outgrowth of early granule cells by influencing neurite elongation. In contrast, NT3 alters the morphology of outgrowth. Collectively, these findings suggest that regulation of neurotrophin receptors during cerebellar development is important for the timing and morphology of axonal growth. In the developing cerebellum, young granule neurons in the external germinal layer respond preferentially to BDNF, while mature neurons within the inner portion of the cerebellum respond preferentially to NT3. Here we show that this anatomic distinction reflects a developmentally regulated switch at the level of neurotrophin receptor gene expression. The salient feature of the developmental switch is a change in the ration of mRNA transcripts encoding functional BDNF and NT3 receptor tyrosine kinases. The ratio of the BDNF receptor trkB to the NT3 receptor trkC reverses from 5:1 in neonatal cerebellum to 1:3 in adult cerebellum. TrkB and TrkC are closely related transmembrane tyrosine protein kinases. However, activation of BDNF and NT3 receptors in cerebellar granule neurons do not give equivalent biological responses. In aggregate cell culture and single cell assays, BDNF enhances axonal outgrowth of early granule cells by influencing neurite elongation. In contrast, NT3 alters the morphology of outgrowth. Collectively, these findings suggest that regulation of neurotrophin receptors during cerebellar development is important for the timing and morphology of axonal growth.

We have undertaken a quantitative analysis of the mouse olfactory bulb to address several major questions concerning the development of neural circuitry in the postnatal mammalian brain. These are: (1) To what degree are new elements and circuits added during maturation? (2) How long do such processes go on? and (3) Does postnatal development involve a net addition of circuits and their constituent elements, or is there elimination of some portion of an initial surfeit? Using male mice of known age, weight, and length, we measured the overall size of the bulb, the numbers of processing units (glomeruli) within the bulb, the extent and complexity of postsynaptic dendrites within the glomeruli, and the number of synapses in different regions of the bulb. Between birth and the time mice reach sexual maturity at 6-7 weeks of age, the bulb increases in size by a factor of 8, the number of glomeruli by a factor of 4-5, the length of mitral cell dendritic branches by a factor of 11, and the number of glomerular and extraglomerular synapses by factors of 90 and 170, respectively. Each of these parameters increases steadily from birth, in concert with the enlargement of the olfactory mucosa, the overall growth of the brain, and indeed, of the entire animal. We found no evidence of an initial surfeit of processing units, dendritic branches, or synapses. Further elaboration of neural circuitry by each of these measures is also apparent from the time of sexual maturity until the animals reach their full adult size at about 10-12 weeks of age. The developmental strategy in this part of the mouse brain evidently involves prolonged construction that persists until the growth of the body is complete. This ongoing elaboration of neural circuitry in the postnatal mammalian brain may be relevant to understanding a number of unexplained developmental phenomena, including critical periods, the ability of the juvenile brain to recover from injuries that would cause severe and permanent deficits in older animals, and the special ability of the maturing brain to encode large amounts of new information.

No abstract

Abstract. Identified neurons and glial cells in a parasympathetic ganglion were observed in situ with video-enhanced microscopy at intervals of up to 130 d in adult mice. Whereas the number and position of glial cells associated with particular neurons did not change over several hours, progressive differences were evident over intervals of weeks to months. These changes involved differences in the location of gliai nuclei on the neuronal surface, differences in the apparent number of glial nuclei associated with each neuron, and often both. When we examined the arrangement of neurons and glial cells in the electron microscope, we also found that presynaptic nerve terminals are more prevalent in the vicinity of glial nuclei than elsewhere on the neuronal surface. The fact that glial nuclei are associated with preganglionic endings, together with the finding that the position and number of glial nuclei associated with identified neurons gradually changes, is in accord with the recent observation that synapses on these neurons are normally subject to ongoing rearrangement (Purves, D., J. T. Voyvodic, L. Magrassi, and H. Yawo. 1987. 238:1122-1126). By the same token, the present results suggest that glial cells are involved in synaptic remodeling. Science (Wash. DC). N'EURONS are invariably associated with glial cells. In some instances, the functional significance of the association is clear, as in the case of axon myelination by Schwann cells or oligodendrocytes (Wood and Bunge, 1984;Bunge, 1986). In most instances, however, the functional role of glia is less clear; certainly, this is true in mammalian autonomic ganglia, in which the principal neurons are invested by gila called satellite cells (Gabella, 1976;Pannese, 1981).In the present report, we have examined glial cells in a mouse autonomic ganglion with the aim of assessing the normal plasticity of the relationship between neurons and gila. In carrying out this work, we have taken advantage of the relatively simple structure of mouse salivary duct ganglia to monitor selected neurons and their associated glial cells over intervals of up to several months in situ. Using the same techniques previously used to follow individual neurons and their synaptic contacts over time , we evaluated the number and position of glial cells associated with identified neurons as a function of the interval between observations. Our results indicate that the relationship between neurons and glial cells gradually changes. Moreover, when we examined these cells with the electron microscope, we found that preganglionic terminals are preferentially located in the vicinity of glial nuclei. The prevalence of synapPortions of this work have appeared in abstract form (1987. Soc. Neurosci. ,4bstr. 13:1008 ses near glial nuclei, taken together with the observation that glial nuclear position gradually changes, implies that glial cells are active participants in the process of synaptic rearrangement. Materials and MethodsYoung adult male mice (CF1 strain; 25-30 g) were anesthetized with ...

We have monitored the pattern of identified glomeruli in the olfactory bulbs of newborn, juvenile, and adult mice over intervals of several hours to several weeks. Our purpose was to assess the development and stability of these complex units in the mammalian brain. Glomeruli can be observed by vital fluorescent staining and laser-scanning confocal microscopy without causing acute or long-term damage to brain tissue. Repeated observation of bulbs in the same animals between birth and 3 weeks of age showed that this region of the brain develops by progressive addition of these units to the original population. This increment occurs by the genesis of smaller new glomeruli between larger existing ones; no elimination of glomeruli was observed during this process. Finally, no addition (or loss) of glomeruli occurred in adult animals over a 2 week interval; once established, the number, size, and pattern of glomeruli are evidently stable.