摘要:

AbstractThe Nerve Growth Factor (NGF) is the progenitor of a family of growth factors which is still expanding. The history of its discovery is very colorful; it is a rare combination of scientific reasoning, intuition, fortuities, and good luck. In addition, I believe that the collaboration of three scientists with very different backgrounds contributed to the success: I had grown up in a laboratory of experimental embryology, Dr. Levi‐Montalcini came from neurology, and Dr. Stanley Cohen was from biochemistry.The decision where to begin the history of a discovery is always arbitrary. I shall give my reasons why I begin this story with my wing bud extirpations on chick embryos and the analysis of the effects of the operation on the development of spinal nerve centers, published in 1934. Of course, I am aware of the fact that the analysis of neurogenesis had been pioneered by Dr. R. G. Harrison and his students at Yale University since the beginning of this century. It should be mentioned that their experiments had been done on amphibian embryos. My own interest in problems of neurogenesis dates back to my Ph.D. thesis in the Zoology Department of Professor H. Spemann at the University of Freiburg in (the Federal Republic of) Germany; it dealt with the influence of the nervous system on the development of limbs in frog embryos. After I had obtained some inconclusive results I did the crucial experiment of producing nerveless legs. I removed the lumbar part of the spinal cord and the spinal ganglia before the outgrowth of nerve fibers. The nerveless legs developed normally in every respect, but the muscles atrophied eventuall

ISSN:0022-3034    

DOI:10.1002/neu.480240702

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractAfter crushing one optic nerve in a bony fish, retinal fibers regenerate to both tecta. Anterograde labelling indicates that the ipsilaterally regenerating fibers have a rather straight growth, apparently along the undamaged fibers of the contralateral retina. In contrast, the contralaterally regenerating fibers deviate widely from a straight course. Retrograde labelling shows a mirror‐symmetric distribution of regenerated ipsilateral and resident contralateral ganglion cells in a comparable annulus. In contrast, ganglion cells in the regenerated contralateral retina show no topological order after comparable small Dil applications to the ventrolateral tectum. These data suggest that regenerating fibers can orient on the undisturbed, contralateral fibers. © 1993 John Wiley&Sons, I

ISSN:0022-3034    

DOI:10.1002/neu.480240703

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractBirdsong is a learned vocal behavior used in intraspecific communication. The motor pathway serving learned vocalizations includes the forebrain nuclei NIf, HVC, and RA; RA projects to midbrain and brain stem areas that control the temporal and acoustic features of song. Nucleus Uvaeformis of the thalamus (Uva) sends input to two of these forebrain nuclei (NIf and HVC) but has not been thought to be important for song production. We used three experimental approaches to reexamine Uva's function in adult male zebra finches. (1) Electrical stimulation applied to Uva activated HVC and the vocal motor pathway, including tracheosyringeal motor neurons that innervate the bird's vocal organ. (2) Bilateral lesions of Uva including the dorso‐medial portion of the nucleus affected the normal temporal organization of song. (3) Chronic multiunit recordings from Uva during normal song and calls show bursts of premotor activity that lead the onset of some song components, and also larger bursts that mark the end of complete song motifs. These results implicate Uva in the production of learned vocalizations, and further suggest that Uva contributes more to the temporal structure than to the acoustic characteristics of song. © 1993 John Wiley&Sons, I

ISSN:0022-3034    

DOI:10.1002/neu.480240704

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe number and the surface density of cells immunoreactive for the specific astrocytic marker glial fibrillary acidic protein (GFAP), were evaluated in both the hilus of the dentate gyrus and the granular layer of the vermis of the cerebellar cortex of adult female rats during the different phases of the estrous cycle, after ovariectomy and after the pharmacological administration of estradiol and/or progesterone to overiectomized rats. Although no significant differences were detected in the number of immunoreactive cells among the different experimental groups studied, their surface density showed significant changes in the hilus of the dentate gyrus. The surface density of immunoreactive cells was increased in the afternoon of proestrus and on the morning of estrus compared to the morning of proestrus, diestrus, and metestrus, was decreased after ovariectomy, and showed a dose‐dependent increase in ovariectomized rats injected with 17β estradiol (1, 10, or 300 μg/rat), alone or in combination with progesterone (500 μg/rat). In contrast, it was not affected by the administration of 17β estradiol (300 μg/rat). The surface density of immunoreactive cells was significantly increased over control values by 5 h after the injection of 17β estradiol (300 μg/rat) and as early as 1 h after the administration of progesterone. The separate injection of either 17β estradiol or progesterone had smaller effects on the surface density of immunoreactive cells than did the administration of both hormones together. The surface density of GFAP‐immunoreactive cells reached maximal values by 24 h after the administration of 17β estradiol and/or progesterone and returned to control levels by 48 h after the combined injection of progesterone and 17β estradiol, while in the rats that were injected with only one of the two hormones, the surface density of immunoreactive cells remained over control values for at least 9 days. No such hormonal effects on GFAP‐immunoreactive cells were observed in the cerebellar cortex. © 1993 John

ISSN:0022-3034    

DOI:10.1002/neu.480240705

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe effect of castration and steroid replacement on the intracellular partitioning of the androgen receptor in the brain of the male Syrian hamster was determined using immunocytochemistry. Androgen receptors were visualized using the PG‐21 antibody (G. S. Prins) on 40‐μm coronal brain sections from hamsters perfused with 4% paraformaldehyde with or without 0.4% glutaraldehyde. Control studies confirmed antibody specificity in gonad‐intact and castrate males. In the normal adult male, androgen receptor immunocytochemistry reveals intense staining confined to the cell nucleus. Castration caused a gradual increase in cytoplasmic labelling within 2 weeks, accompanied by a reduction in nuclear staining intensity in androgen receptor‐containing neurons throughout the brain. Cytoplasmic androgen receptor staining was eliminated after treatment of orchidectomized males for only 8 h with exogenous testosterone. Likewise, long‐term exposure to testosterone and dihydrotestosterone, a nonaromatizable androgen, maintained nuclear androgen receptor immunoreactivity. However, exposure to low physiologic concentrations of estrogen was not effective in this regard. In addition, we determined that nuclear androgen receptor immunoreactivity decreases in response to inhibitory short‐day photoperiod, but without an increase in cytoplasmic immunostaining. This appears to be due to the decrease in androgen production by the testis, rather than a direct photoperiodic effect, because testosterone supplementation to short‐day males restored the intensity of nuclear androgen receptor immuno‐reactivity to levels comparable to those in the intact male. These findings are compatible with a new model for the intracellular localization of androgen receptors, in which a subset of unoccupied receptors is located in the cell cytoplasm in the absence of ligand. They further demonstrate the repartitioning of such cytoplasmic receptors, thereby confirming and extending previous observations using biochemical techniques on the regulation of neuronal androgen receptors. © 1993 Joh

ISSN:0022-3034    

DOI:10.1002/neu.480240706

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractAntibodies to channel proteins and specific peptide sequences have been previously used to localize voltage‐activated sodium channels in the rat brain. Here we describe the first localization of sodium channels in an insect nervous system using a site‐directed antibody. The mesothoracic ganglion of the cockroach was stained with an antibody to the highly conserved SP19 sequence. Antibody labelling was visualized by light microscopy using the avidin/biotin method on was sections, and transmission electron microscopy of immunogold‐labelled thin sections. Central ganglia of insects contain clearly separated regions of cell bodies, synaptic neuropil, axon tracts, and nerves. Antibody staining by light microscopy was limited to neurons, and was intense in axons throughout the ganglion and nerves. Staining was also strong in the cytoplasm, but not the nuclei, of many neuronal cell bodies. Neuropil regions were relatively lightly labelled. These findings can be correlated with the known electrophysiology of the ganglion. Electron microscopy detected sodium channels in areas surrounding axons, probably including axon membranes and enveloping glial cell membranes. Axonal mitochondria were also heavily labelled, suggesting a sodium channel transport function for these organelles. © 1993 John Wiley&Son

ISSN:0022-3034    

DOI:10.1002/neu.480240707

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractB50/GAP‐43 has been implicated in neural plasticity, development, and regeneration. Several studies of axonally transported proteins in the optic nerve have shown that this protein is synthesized by developing and regenerating retinal ganglion cells in mammals, amphibians, and fish. However, previous studies using immunohistochemistry to localize B50/GAP‐43 in retina have shown that this protein is found in the inner plexiform layer in adults. Since the inner plexiform layer contains the processes of amacrine cells, ganglion cells, and bipolar cells to determine which cells in the retina express B50/GAP‐43, we have now usedin situhybridization to localize the mRNA that codes for this protein in the developing rat retina. We have found that B50/GAP‐43 is expressed primarily by cells in the retinal ganglion cell layer as early as embryonic day 15, and until 3 weeks postnatal. Some cells in the inner nuclear layer, possibly a subclass of amacrine cells, also express B50/GAP‐43 protein and mRNA; however, the other retinal neurons–bipolar cells, photoreceptors, and horizontal cells express little, if any, B50/GAP‐43 at any stage in their development. Early in development, the protein appears in the somata and axons of ganglion cells, while later in development, B50/GAP‐43 becomes concentrated in the inner plexiform layer, where it continues to be expressed in adult animals. These results are discussed in terms of previous proposals as to the functions of this molecule. © 1993 John

ISSN:0022-3034    

DOI:10.1002/neu.480240708

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractPeripheral nerve injury results in the increased synthesis and axonal trasnport of the growth‐associated protein GAP‐43 in dorsal root ganglion (DRG) neurons, coincident with regenerative growth of the injured peripheral axon branches. To determine wheter the injury‐associated signalling mechanism which leads to GAP‐43 induction also operates through the central branches of DRG axons, we used immunocytochemistry to compare the expression of GAP‐43 in adult rat DRG neurons 2 weeks after dorsal root crush lesions (central axotomy) or peripheral nerve crush lesions (peripheral axotomy). In uninjured ganglia, a subpopulation of smaller DRG neurons expresses moderate levels of GAP‐43, whereas larger neurons generally do not. At 2 weeks following peripheral axotomy, virtually all axotomized neurons, large and small, express high levels of GAP‐43. At 2 weeks following dorsal root lesions, no increase in GAP‐43 expression is detected. Thus, the injury‐associated up‐regulation of GAP‐43 expression in DRG neurons is triggered by a mechanism that is responsive to injury of only the peripheral, and not the central, axon branches. These findings support the hypothesis that GAP‐43 induction in DRG neurons is caused by disconnection from peripheral target tissue, not by axon injury per se. © 1

ISSN:0022-3034    

DOI:10.1002/neu.480240709

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe jump response to a light‐off startle stimulus inDrosophila melanogasteroccurs when the Giant Fiber (GF), a neuron descending from the brain to the thorax, drives the jump (tergotrochanteral) muscle motorneuron (TTMn). Nonjumping mutants have been isolated in which this response is disrupted. Flies bearing the X‐chromosome mutationPassover(Pas) fail to jump in response to a light‐off stimulus, and electrical stimulation of the GF in the brain no longer elicits the normal response in the TTM. We have used retrograde HRP labelling to examine the TTMn motorneuron in wild‐type flies and in a variety of newly identifiedPasalleles. In wild type the medial branch (MB) of the TTMn has an extensive region of apposition with the GF. InPasalleles, there is a general reduction in anterior‐posterior (A‐P) extent of the medial branch but not of the posterior branch. Nevertheless,Pasalleles usually leave the TTMn close enough to the GF so that contact would not be precluded. In flies carrying a particular deficiency ofPas,Df(1) 16–3–22, includingPas/Df(1) 16–3–22heterozygotes, there can be extensive growth of the medial branch including a contralateral projection; these heterozygotes have more than the normal amount of overlap between the GF and the TTMn. This phenotype, originally ascribed toPasmutants, is associated withDf(1) 16–3–22, but not with other deletions of thePasgene. The driving of the TTMn by the GF is defective in mutant genotypes with extensive medial branches as well as in mutants where GF‐TTMn contact is reduced. The fact that the TTMn grows into its normal synaptic region in mutant genotypes, but the GF pathway functions abnormally suggests that pathfinding by the TTMn is not impaired. It is more likely that thePasmutation disrupts cell recognition, synaptogenesis, or synaptic function in the TTMn or its presynaptic partners. ©

ISSN:0022-3034    

DOI:10.1002/neu.480240710

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractSynaptic repression, the inability of synaptic junctions to generate normal‐sized postsynaptic potentials under normal physiological conditions, is reported here for crayfish neuromuscular synapses. The synapses in the superficial flexor muscle system of the crayfish change their efficiency in generating a postsynaptic response as a result of a specific alteration in their immediate environment. When the superficial flexor nerve is cut halfway into the target muscle field and the lateral muscle fibers are removed, the intact medial synapses do not generate normal‐sized junction potentials (JP) at the 17° –19°C temperature of the Ringers solution. JPs cannot be recorded in 83% of the muscle fibers at 2 weeks after the operation and of the few JPs that can be detected, 80% are smaller than 1 mV in size. By 8 weeks after the operation, JPs were detected in 55% of the muscle fibers, and now only 46% of these are smaller than 1 mV. When the lateral muscle fibers are left in place during the original operation, providing a target area for the cut nerve to grow into, JPs were then detected in 60%–80% of all medial fibers at all time periods after the operation; their size profile, with 10%–25% of the muscle fibers having JP's less than 1 mV, was similar to control values. These results suggest that the efficiency of these synaptic contacts become affected as a result of partial axotomy and removal of the target area of the cut branches of the axons. © 1993 John Wil

ISSN:0022-3034    

DOI:10.1002/neu.480240711

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY