The perception of song is vital to the reproductive success of both male and female songbirds. Several neural structures underlying this perception have been identified by examining expression of immediate early genes (IEGs) following the presentation of conspecific or heterospecific song. In the few avian species investigated, areas outside of the circuit for song production contain neurons that are active following song presentation, specifically the caudal hyperstriatum ventrale (cHV) and caudomedial neostriatum (NCM). While studied in detail in the male zebra finch, IEG responses in these neural substrates involved in song perception have not been quantified in females. Therefore, adult female zebra finches were presented with zebra finch song, nonzebra finch song, randomly generated tones, or silence for 30 min. One hour later they were sacrificed, and their brains removed, sectioned, and immunocytochemically processed for FOS expression. Animals exposed to zebra finch song had a significantly higher density of FOS-immunoreactive cells in the NCM than those presented with other songs, tones, or silence. Neuronal activation in the cHV was equivalent in birds that heard zebra finch and non-zebra finch song, expression that was higher than that observed in the groups that heard no song. Interestingly, the hippocampus (HP) and adjacent parahippocampal area (AHP) were activated in a manner comparable to the NCM. These results suggest a general role for the cHV in song perception and a more specific role for the NCM and HP/AHP in facilitating recognition of and responsiveness to species-specific song in female zebra finches.
{"title":"The hippocampus and caudomedial neostriatum show selective responsiveness to conspecific song in the female zebra finch.","authors":"D. J. Bailey, J. Rosebush, J. Wade","doi":"10.1002/NEU.10070","DOIUrl":"https://doi.org/10.1002/NEU.10070","url":null,"abstract":"The perception of song is vital to the reproductive success of both male and female songbirds. Several neural structures underlying this perception have been identified by examining expression of immediate early genes (IEGs) following the presentation of conspecific or heterospecific song. In the few avian species investigated, areas outside of the circuit for song production contain neurons that are active following song presentation, specifically the caudal hyperstriatum ventrale (cHV) and caudomedial neostriatum (NCM). While studied in detail in the male zebra finch, IEG responses in these neural substrates involved in song perception have not been quantified in females. Therefore, adult female zebra finches were presented with zebra finch song, nonzebra finch song, randomly generated tones, or silence for 30 min. One hour later they were sacrificed, and their brains removed, sectioned, and immunocytochemically processed for FOS expression. Animals exposed to zebra finch song had a significantly higher density of FOS-immunoreactive cells in the NCM than those presented with other songs, tones, or silence. Neuronal activation in the cHV was equivalent in birds that heard zebra finch and non-zebra finch song, expression that was higher than that observed in the groups that heard no song. Interestingly, the hippocampus (HP) and adjacent parahippocampal area (AHP) were activated in a manner comparable to the NCM. These results suggest a general role for the cHV in song perception and a more specific role for the NCM and HP/AHP in facilitating recognition of and responsiveness to species-specific song in female zebra finches.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74632957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Previous studies have shown that sensory target tissues induce neuropeptides in naïve sensory neurons, and that activin and bone morphogenetic proteins (BMPs) are capable of inducing neuropeptides associated with nociception in embryonic sensory neurons in vitro. The goal of the present study was to learn if these ligands were available in native sensory neuron target tissues at correct developmental periods to play this inductive role in vivo. Sensory neurons initially contact their peripheral target tissues and begin to express neuropeptides during late embryogenesis, and we demonstrate that activin and BMPs are present in the embryo and neonate to regulate sensory neuron differentiation. Native embryonic and neonatal target tissues were analyzed by immunoblot and immunohistochemical studies using ligand-specific antibodies. Although activin was easily solubilized, BMPs were detected only after high salt extraction, suggesting that BMPs were bound to extracellular moieties and were capable of acting only locally in native tissues. One inhibitor, noggin, was present in both embryonic skin and muscle. In combination, these data suggest that neuronal differentiation is unlikely to be regulated by simple expression of ligand, but that the functional availability of ligand is a critical component confering biological activity.
{"title":"Activin and bone morphogenetic proteins are present in perinatal sensory neuron target tissues that induce neuropeptides.","authors":"A. K. Hall, R. Burke, Malini Anand, K. Dinsio","doi":"10.1002/NEU.10068","DOIUrl":"https://doi.org/10.1002/NEU.10068","url":null,"abstract":"Previous studies have shown that sensory target tissues induce neuropeptides in naïve sensory neurons, and that activin and bone morphogenetic proteins (BMPs) are capable of inducing neuropeptides associated with nociception in embryonic sensory neurons in vitro. The goal of the present study was to learn if these ligands were available in native sensory neuron target tissues at correct developmental periods to play this inductive role in vivo. Sensory neurons initially contact their peripheral target tissues and begin to express neuropeptides during late embryogenesis, and we demonstrate that activin and BMPs are present in the embryo and neonate to regulate sensory neuron differentiation. Native embryonic and neonatal target tissues were analyzed by immunoblot and immunohistochemical studies using ligand-specific antibodies. Although activin was easily solubilized, BMPs were detected only after high salt extraction, suggesting that BMPs were bound to extracellular moieties and were capable of acting only locally in native tissues. One inhibitor, noggin, was present in both embryonic skin and muscle. In combination, these data suggest that neuronal differentiation is unlikely to be regulated by simple expression of ligand, but that the functional availability of ligand is a critical component confering biological activity.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84086877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The courtship solicitation display (CSD) of the female canary is a model to study estrogen dependent auditory preferences for male songs. The forebrain auditory-vocal nucleus, HVC, is part of the circuit that determines such preferences. To further develop this model we show that bilateral excitotoxic lesions of the medial part of HVC involving between 18-60% of the bilateral nucleus are behaviorally effective while complete unilateral lesions are not. Further, we show that animals recover their song preferences over a period of several months after the lesion. This functional recovery does not involve anatomical recovery of the HVC. Even 9 months after the lesion, the HVC size of these females was similar to that of females sacrificed 2 days after the lesion and thus was 40 +/- 8% smaller compared to normal females. Further, ipsilaterally, the lesion procedure transiently disturbed the neurochemistry, such as GAD-mRNA expression, in the part of HVC that did not undergo cell death. These results suggest that the integrity of the lateral part of at least one HVC is required to perform CSD in response to relevant auditory stimuli.
{"title":"Recovery of song preferences after excitotoxic HVC lesion in female canaries.","authors":"F. Halle, M. Gahr, A. Pieneman, M. Kreutzer","doi":"10.1002/NEU.10058","DOIUrl":"https://doi.org/10.1002/NEU.10058","url":null,"abstract":"The courtship solicitation display (CSD) of the female canary is a model to study estrogen dependent auditory preferences for male songs. The forebrain auditory-vocal nucleus, HVC, is part of the circuit that determines such preferences. To further develop this model we show that bilateral excitotoxic lesions of the medial part of HVC involving between 18-60% of the bilateral nucleus are behaviorally effective while complete unilateral lesions are not. Further, we show that animals recover their song preferences over a period of several months after the lesion. This functional recovery does not involve anatomical recovery of the HVC. Even 9 months after the lesion, the HVC size of these females was similar to that of females sacrificed 2 days after the lesion and thus was 40 +/- 8% smaller compared to normal females. Further, ipsilaterally, the lesion procedure transiently disturbed the neurochemistry, such as GAD-mRNA expression, in the part of HVC that did not undergo cell death. These results suggest that the integrity of the lateral part of at least one HVC is required to perform CSD in response to relevant auditory stimuli.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78497349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Estrogen modulates many features of the sympathetic nervous system, including cell numbers and ganglion synapses, and can induce uterine sympathetic nerve degeneration. However, distributions of estrogen receptors alpha and beta within sympathetic neurons have not been described, and their regulation by target tissue or estrogen levels has not been explored. We used immunofluorescence and retrograde tracing to define estrogen receptor expression in sympathetic neurons at large in pre- and paravertebral ganglia and in those projecting to the uterine horns. Estrogen receptor alpha immunoreactivity was present in 29 +/- 1%, while estrogen receptor beta was expressed by 92 +/- 1% of sympathetic neurons at large. The proportions of neurons expressing these receptors were comparable in the superior cervical and thoraco-lumbar paravertebral ganglia from T11 through L5, and in the suprarenal, celiac, and superior mesenteric prevertebral ganglia. Injections of FluoroGold into the uterine horns resulted in labeled neurons, with peak occurrences in T13, L1, and the suprarenal ganglion. Uterine-projecting neurons showed small but significantly greater incidence of estrogen receptor beta expression relative to the neuronal population at large, whereas the proportion of uterine-projecting neurons with estrogen receptor alpha-immunoreactivity was nearly threefold greater. Numbers of estrogen receptor-expressing neurons were not altered by acute estrogen administration. We conclude that the vast majority of sympathetic neurons express estrogen receptor beta immunoreactive protein, whereas a smaller, presumably overlapping subset expresses the estrogen receptor alpha. Expression of the latter apparently can be enhanced by target-mediated mechanisms.
{"title":"Distributions of estrogen receptors alpha and beta in sympathetic neurons of female rats: enriched expression by uterine innervation.","authors":"E. Zoubina, Peter G. Smith","doi":"10.1002/NEU.10064","DOIUrl":"https://doi.org/10.1002/NEU.10064","url":null,"abstract":"Estrogen modulates many features of the sympathetic nervous system, including cell numbers and ganglion synapses, and can induce uterine sympathetic nerve degeneration. However, distributions of estrogen receptors alpha and beta within sympathetic neurons have not been described, and their regulation by target tissue or estrogen levels has not been explored. We used immunofluorescence and retrograde tracing to define estrogen receptor expression in sympathetic neurons at large in pre- and paravertebral ganglia and in those projecting to the uterine horns. Estrogen receptor alpha immunoreactivity was present in 29 +/- 1%, while estrogen receptor beta was expressed by 92 +/- 1% of sympathetic neurons at large. The proportions of neurons expressing these receptors were comparable in the superior cervical and thoraco-lumbar paravertebral ganglia from T11 through L5, and in the suprarenal, celiac, and superior mesenteric prevertebral ganglia. Injections of FluoroGold into the uterine horns resulted in labeled neurons, with peak occurrences in T13, L1, and the suprarenal ganglion. Uterine-projecting neurons showed small but significantly greater incidence of estrogen receptor beta expression relative to the neuronal population at large, whereas the proportion of uterine-projecting neurons with estrogen receptor alpha-immunoreactivity was nearly threefold greater. Numbers of estrogen receptor-expressing neurons were not altered by acute estrogen administration. We conclude that the vast majority of sympathetic neurons express estrogen receptor beta immunoreactive protein, whereas a smaller, presumably overlapping subset expresses the estrogen receptor alpha. Expression of the latter apparently can be enhanced by target-mediated mechanisms.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78443319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Kuang, Shandra A. Doran, Richard J. A. Wilson, G. Goss, J. Goldberg
Oxygen (O(2)) is one of the most important environmental factors that affects both physiological processes and development of aerobic animals, yet little is known about the neural mechanism of O(2) sensing and adaptive responses to low O(2) (hypoxia) during development. In the pond snail, Helisoma trivolvis, the first embryonic neurons (ENC1s) to develop are a pair of serotonergic sensory-motor cells that regulate a cilia-driven rotational behavior. Here, we report that the ENC1-ciliary cell circuit mediates an adaptive behavioral response to hypoxia. Exposure of egg masses to hypoxia elicited a dose-dependent and reversible acceleration of embryonic rotation that mixed capsular fluid, thereby facilitating O(2) diffusion to the embryo. The O(2) partial pressures (Po(2)) for threshold, half-maximal, and maximal rotational response were 60, 28, and 13 mm Hg, respectively. During hypoxia, embryos relocated to the periphery of the egg masses where higher Po(2) levels occurred. Furthermore, intermittent hypoxia treatments induced a sensitization of the rotational response. In isolated ciliary cells, ciliary beating was unaffected by hypoxia, suggesting that in the embryo, O(2) sensing occurs upstream of the motile cilia. The rotational response of embryos to hypoxia was attenuated by application of the serotonin receptor antagonist, mianserin, correlated to the development of ENC1-ciliary cell circuit, and abolished by laser-ablation of ENC1s. Together, these data suggest that ENC1s are unique oxygen sensors that may provide a good single cell model for the examination of mechanistic, developmental, and evolutionary aspects of O(2) sensing.
氧(O(2))是影响需氧动物生理过程和发育的最重要的环境因素之一，但在发育过程中对O(2)的感知和低氧(缺氧)适应性反应的神经机制尚不清楚。在池塘蜗牛Helisoma trivolvis中，最早发育的胚胎神经元(ENC1s)是一对血清素能感觉运动细胞，它们调节纤毛驱动的旋转行为。在这里，我们报道了enc1 -纤毛细胞回路介导对缺氧的适应性行为反应。暴露于低氧的卵团引发了一个剂量依赖性和可逆的胚胎旋转加速，混合荚膜液，从而促进O(2)向胚胎扩散。阈值、半最大值和最大旋转响应的O(2)分压(Po(2))分别为60、28和13 mm Hg。在缺氧的情况下，胚胎迁移到卵群的外围，那里的Po(2)水平较高。此外，间歇性缺氧治疗诱导旋转反应敏化。在离体纤毛细胞中，纤毛跳动不受缺氧影响，这表明在胚胎中，O(2)感知发生在运动纤毛的上游。应用5 -羟色胺受体拮抗剂米安色林可减弱胚胎对缺氧的旋转反应，该反应与enc1 -纤毛细胞回路的发育有关，并可通过激光消融enc1而消除。综上所述，这些数据表明enc1是独特的氧传感器，可以为O(2)传感的机制、发育和进化方面的研究提供一个良好的单细胞模型。
{"title":"Serotonergic sensory-motor neurons mediate a behavioral response to hypoxia in pond snail embryos.","authors":"S. Kuang, Shandra A. Doran, Richard J. A. Wilson, G. Goss, J. Goldberg","doi":"10.1002/NEU.10071","DOIUrl":"https://doi.org/10.1002/NEU.10071","url":null,"abstract":"Oxygen (O(2)) is one of the most important environmental factors that affects both physiological processes and development of aerobic animals, yet little is known about the neural mechanism of O(2) sensing and adaptive responses to low O(2) (hypoxia) during development. In the pond snail, Helisoma trivolvis, the first embryonic neurons (ENC1s) to develop are a pair of serotonergic sensory-motor cells that regulate a cilia-driven rotational behavior. Here, we report that the ENC1-ciliary cell circuit mediates an adaptive behavioral response to hypoxia. Exposure of egg masses to hypoxia elicited a dose-dependent and reversible acceleration of embryonic rotation that mixed capsular fluid, thereby facilitating O(2) diffusion to the embryo. The O(2) partial pressures (Po(2)) for threshold, half-maximal, and maximal rotational response were 60, 28, and 13 mm Hg, respectively. During hypoxia, embryos relocated to the periphery of the egg masses where higher Po(2) levels occurred. Furthermore, intermittent hypoxia treatments induced a sensitization of the rotational response. In isolated ciliary cells, ciliary beating was unaffected by hypoxia, suggesting that in the embryo, O(2) sensing occurs upstream of the motile cilia. The rotational response of embryos to hypoxia was attenuated by application of the serotonin receptor antagonist, mianserin, correlated to the development of ENC1-ciliary cell circuit, and abolished by laser-ablation of ENC1s. Together, these data suggest that ENC1s are unique oxygen sensors that may provide a good single cell model for the examination of mechanistic, developmental, and evolutionary aspects of O(2) sensing.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75754902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We investigated calretinin expression in cerebellar granule cells of 30-day-old leaner mice to understand possible changes in calcium homeostasis due to the calcium channel mutation that these mice carry. Quantitative in situ hybridization histochemistry showed decreased calretinin mRNA expression in the leaner cerebellum. Immunohistochemical staining also revealed decreased calretinin immunoreactivity in the leaner cerebellum. To exclude the effect of granule cell loss that occurs in the leaner mouse when comparing cerebellar calretinin expression, the number of granule cells per unit area in the cerebellum was compared to the wild-type cerebellum. Granule cell counts per unit area of cerebellum revealed similar numbers of granule cells present in wild-type and leaner mice. Laser capture microdissection (LCM) was employed to obtain an equal number of granule cells from wild-type and leaner mice. Western blot analysis with LCM-procured cerebellar granule cells showed decreased calretinin expression in leaner granule cells. These results indicate that there is an absolute decrease in calretinin expression in leaner granule cells even when granule cell loss is taken into account. Decreased calretinin expression in leaner granule cells may contribute to altered calcium buffering capacity. This alteration could be an adaptive change due to the calcium channel dysfunction, and may result in abnormal neuronal excitability and gene expression.
{"title":"Decreased calretinin expression in cerebellar granule cells in the leaner mouse.","authors":"Sang-Soep Nahm, D. Tomlinson, L. Abbott","doi":"10.1002/NEU.10067","DOIUrl":"https://doi.org/10.1002/NEU.10067","url":null,"abstract":"We investigated calretinin expression in cerebellar granule cells of 30-day-old leaner mice to understand possible changes in calcium homeostasis due to the calcium channel mutation that these mice carry. Quantitative in situ hybridization histochemistry showed decreased calretinin mRNA expression in the leaner cerebellum. Immunohistochemical staining also revealed decreased calretinin immunoreactivity in the leaner cerebellum. To exclude the effect of granule cell loss that occurs in the leaner mouse when comparing cerebellar calretinin expression, the number of granule cells per unit area in the cerebellum was compared to the wild-type cerebellum. Granule cell counts per unit area of cerebellum revealed similar numbers of granule cells present in wild-type and leaner mice. Laser capture microdissection (LCM) was employed to obtain an equal number of granule cells from wild-type and leaner mice. Western blot analysis with LCM-procured cerebellar granule cells showed decreased calretinin expression in leaner granule cells. These results indicate that there is an absolute decrease in calretinin expression in leaner granule cells even when granule cell loss is taken into account. Decreased calretinin expression in leaner granule cells may contribute to altered calcium buffering capacity. This alteration could be an adaptive change due to the calcium channel dysfunction, and may result in abnormal neuronal excitability and gene expression.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76588870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuronal growth cones are capable of sophisticated discrimination of environmental cues, on cell surfaces and in the extracellular matrix, to accomplish navigation during development (generation) and following nervous system injury (regeneration). Choices made by growth cones are commonly examined using tissue culture paradigms in which molecules of interest are purified and substratum-bound. From observations of growth cone behaviors using these paradigms, assertions are made about choices neuronal growth cones may make in vivo. However, in many cases, the binding, interactions, and conformations of these molecules have not been determined. In the present study, we investigated the binding characteristics of two commonly studied outgrowth regulatory molecules: chondroitin sulfate proteoglycans (CSPGs), which are typically inhibitory to neurite outgrowth during development and following nervous system injury, and laminin, which is typically outgrowth promoting for many neuronal types. Using a novel combination of radiolabeling and quantitative fluorescence, we determined the precise concentrations of CSPGs and laminin-1 that were bound separately and together in a variety of choice assays. For identically prepared cultures, we correlated neurite outgrowth behaviors with binding characteristics. The data support-our working hypothesis that neuronal growth cones are guided by the ratio of outgrowth-promoting to outgrowth-inhibiting influences in their environment, i.e., they summate local molecular cues. The response of growth cones to these molecular combinations is most likely mediated by integrins and subsequent activation of signal transduction cascades in growth cones.
{"title":"Binding characteristics of chondroitin sulfate proteoglycans and laminin-1, and correlative neurite outgrowth behaviors in a standard tissue culture choice assay.","authors":"D. Snow, Jeffrey D. Smith, J. Gurwell","doi":"10.1002/NEU.10060","DOIUrl":"https://doi.org/10.1002/NEU.10060","url":null,"abstract":"Neuronal growth cones are capable of sophisticated discrimination of environmental cues, on cell surfaces and in the extracellular matrix, to accomplish navigation during development (generation) and following nervous system injury (regeneration). Choices made by growth cones are commonly examined using tissue culture paradigms in which molecules of interest are purified and substratum-bound. From observations of growth cone behaviors using these paradigms, assertions are made about choices neuronal growth cones may make in vivo. However, in many cases, the binding, interactions, and conformations of these molecules have not been determined. In the present study, we investigated the binding characteristics of two commonly studied outgrowth regulatory molecules: chondroitin sulfate proteoglycans (CSPGs), which are typically inhibitory to neurite outgrowth during development and following nervous system injury, and laminin, which is typically outgrowth promoting for many neuronal types. Using a novel combination of radiolabeling and quantitative fluorescence, we determined the precise concentrations of CSPGs and laminin-1 that were bound separately and together in a variety of choice assays. For identically prepared cultures, we correlated neurite outgrowth behaviors with binding characteristics. The data support-our working hypothesis that neuronal growth cones are guided by the ratio of outgrowth-promoting to outgrowth-inhibiting influences in their environment, i.e., they summate local molecular cues. The response of growth cones to these molecular combinations is most likely mediated by integrins and subsequent activation of signal transduction cascades in growth cones.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81820107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Stewart, M. Mohtashami, P. Rivlin, D. Deitcher, W. Trimble, G. Boulianne
N-ethylmaleimide sensitive fusion protein (NSF) is an ATPase necessary for vesicle trafficking, including exocytosis. Current models hold that NSF is required in a step that readies vesicles for fusion by disassembling postfusion SNARE protein complexes allowing them to participate in further rounds of vesicle cycling. Whereas most organisms have only one NSF isoform, Drosophila has two. dNSF1 is the predominant functional isoform in the adult nervous system. Conditional mutations in the dNSF1 gene, comatose, are paralytic and lead to disruption of synaptic transmission and the rapid accumulation of SNARE complexes in adult flies. This isoform is not required for synaptic transmission in larvae. In contrast, dNSF2 is important at earlier developmental stages, and its broad expression indicates its importance in neural and non-neural tissues alike. To study dNSF2, and to circumvent the lethality of dNSF2 null mutants, we have constructed transgenic flies carrying a dominant negative form of dNSF2. When this construct was expressed in neurons we observed suppression of synaptic transmission, activity-dependent fatigue of transmitter release, and a reduction in the number of releasable vesicles. However, we unexpectedly found that there was no accumulation of SNARE complexes accompanying these physiological phenotypes. Intriguingly, we also found that expression of mutant dNSF2 induced pronounced overgrowth of the neuromuscular junction and some misrouting of axons. These results support the idea that dNSF2 has multiple roles in cellular function and adds that not all of its functions require disassembly of the SNARE complex.
n -乙基马来酰亚胺敏感融合蛋白(NSF)是囊泡运输所需的三磷酸腺苷酶，包括胞吐作用。目前的模型认为NSF是为囊泡融合做准备的一个步骤，通过分解融合后的SNARE蛋白复合物，使其参与进一步的囊泡循环。大多数生物体只有一种NSF亚型，而果蝇却有两种。dNSF1是成人神经系统中主要的功能亚型。在成年果蝇中，dNSF1基因comatose的条件突变会导致瘫痪，并导致突触传递中断和SNARE复合物的快速积累。这种异构体在幼虫的突触传递中是不需要的。相反，dNSF2在早期发育阶段很重要，其广泛表达表明其在神经和非神经组织中的重要性。为了研究dNSF2，并规避dNSF2零突变体的致死性，我们构建了携带dNSF2显性阴性形式的转基因果蝇。当这种结构在神经元中表达时，我们观察到突触传递受到抑制，递质释放的活动依赖性疲劳，以及可释放囊泡数量的减少。然而，我们意外地发现，在这些生理表型中没有SNARE复合物的积累。有趣的是，我们还发现dNSF2突变体的表达诱导了神经肌肉连接处的明显过度生长和轴突的一些错误路线。这些结果支持了dNSF2在细胞功能中具有多种作用的观点，并补充说，并非所有的功能都需要分解SNARE复合体。
{"title":"Dominant-negative NSF2 disrupts the structure and function of Drosophila neuromuscular synapses.","authors":"B. Stewart, M. Mohtashami, P. Rivlin, D. Deitcher, W. Trimble, G. Boulianne","doi":"10.1002/NEU.10059","DOIUrl":"https://doi.org/10.1002/NEU.10059","url":null,"abstract":"N-ethylmaleimide sensitive fusion protein (NSF) is an ATPase necessary for vesicle trafficking, including exocytosis. Current models hold that NSF is required in a step that readies vesicles for fusion by disassembling postfusion SNARE protein complexes allowing them to participate in further rounds of vesicle cycling. Whereas most organisms have only one NSF isoform, Drosophila has two. dNSF1 is the predominant functional isoform in the adult nervous system. Conditional mutations in the dNSF1 gene, comatose, are paralytic and lead to disruption of synaptic transmission and the rapid accumulation of SNARE complexes in adult flies. This isoform is not required for synaptic transmission in larvae. In contrast, dNSF2 is important at earlier developmental stages, and its broad expression indicates its importance in neural and non-neural tissues alike. To study dNSF2, and to circumvent the lethality of dNSF2 null mutants, we have constructed transgenic flies carrying a dominant negative form of dNSF2. When this construct was expressed in neurons we observed suppression of synaptic transmission, activity-dependent fatigue of transmitter release, and a reduction in the number of releasable vesicles. However, we unexpectedly found that there was no accumulation of SNARE complexes accompanying these physiological phenotypes. Intriguingly, we also found that expression of mutant dNSF2 induced pronounced overgrowth of the neuromuscular junction and some misrouting of axons. These results support the idea that dNSF2 has multiple roles in cellular function and adds that not all of its functions require disassembly of the SNARE complex.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74286615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the developing visual system of Xenopus laevis retinal ganglion cell (RGC) axons extend through the brain towards their major target in the midbrain, the optic tectum. Enroute, the axons are guided along their pathway by cues in the environment. In vitro, neurotransmitters have been shown to act chemotropically to influence the trajectory of extending axons and regulate the outgrowth of developing neurites, suggesting that they may act to guide or modulate the growth of axons in vivo. Previous work by Roberts and colleagues (1987) showed that populations of cells within the developing Xenopus diencephalon and mid-brain express the neurotransmitter gamma amino butyric acid (GABA). Here we show that Xenopus RGC axons in the midoptic tract grow alongside the GABAergic cells and cross their GABA immunopositive nerve processes. Moreover, RGC axons and growth cones express GABA-A and GABA-B receptors, and GABA and the GABA-B receptor agonist baclofen both stimulate RGC neurite outgrowth in culture. Finally, the GABA-B receptor antagonist CGP54626 applied to the developing optic projection in vivo causes a dose-dependent shortening of the optic projection. These data indicate that GABA may act in vivo to stimulate the outgrowth of Xenopus RGC axons along the optic tract.
{"title":"GABA and development of the Xenopus optic projection.","authors":"Shane C D Ferguson, S. McFarlane","doi":"10.1002/NEU.10061","DOIUrl":"https://doi.org/10.1002/NEU.10061","url":null,"abstract":"In the developing visual system of Xenopus laevis retinal ganglion cell (RGC) axons extend through the brain towards their major target in the midbrain, the optic tectum. Enroute, the axons are guided along their pathway by cues in the environment. In vitro, neurotransmitters have been shown to act chemotropically to influence the trajectory of extending axons and regulate the outgrowth of developing neurites, suggesting that they may act to guide or modulate the growth of axons in vivo. Previous work by Roberts and colleagues (1987) showed that populations of cells within the developing Xenopus diencephalon and mid-brain express the neurotransmitter gamma amino butyric acid (GABA). Here we show that Xenopus RGC axons in the midoptic tract grow alongside the GABAergic cells and cross their GABA immunopositive nerve processes. Moreover, RGC axons and growth cones express GABA-A and GABA-B receptors, and GABA and the GABA-B receptor agonist baclofen both stimulate RGC neurite outgrowth in culture. Finally, the GABA-B receptor antagonist CGP54626 applied to the developing optic projection in vivo causes a dose-dependent shortening of the optic projection. These data indicate that GABA may act in vivo to stimulate the outgrowth of Xenopus RGC axons along the optic tract.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89814560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Widespread telencephalic neuronal replacement occurs throughout life in birds. We explored the potential relationship between thyroxine (T4) and cell turnover in the adult male zebra finch. We found that many cells in the zebra finch brain, including long-projection neurons in the high vocal center (HVC), stained positively with an antibody to thyroid hormone receptors (TR). Labeling was generally weak in the ventricular zone (VZ) that gives rise to new neurons but some proliferative VZ cells and/or their progeny, identified by [3H]-thymidine labeling, co-labeled with anti-TR antibody. Acute T4 treatment dramatically increased the number of pyknotic and TUNEL-positive cells in HVC and other telencephalic regions. In contrast, degenerating cells were never observed in the archistriatum or sub-telencephalic regions, suggesting that excess T4 augments cell death selectively in regions that show naturally occurring neuronal turnover. VZ mitotic activity was not altered shortly after acute T4 treatment at a dosage that stimulated cell death, although [3H]-labeling intensity per cell was slightly reduced. Moreover, the incorporation rates for neurons formed shortly before or after acute hormone treatment were no different from control values. Chronic T4 treatment resulted in a reduction in the total number of HVC neurons. Thus, hyperthyroidism augmented neuronal death, which was not compensated for by neuronal replacement. Collectively, these results indicate that excess T4 affects adult neuronal turnover in birds, and raises the possibility that thyroxine plays an important role in the postnatal development of the avian brain and vocal behavior.
{"title":"Effects of excess thyroid hormone on cell death, cell proliferation, and new neuron incorporation in the adult zebra finch telencephalon.","authors":"P. Tekumalla, M. Tontonoz, M. A. Hesla, J. Kirn","doi":"10.1002/NEU.10053","DOIUrl":"https://doi.org/10.1002/NEU.10053","url":null,"abstract":"Widespread telencephalic neuronal replacement occurs throughout life in birds. We explored the potential relationship between thyroxine (T4) and cell turnover in the adult male zebra finch. We found that many cells in the zebra finch brain, including long-projection neurons in the high vocal center (HVC), stained positively with an antibody to thyroid hormone receptors (TR). Labeling was generally weak in the ventricular zone (VZ) that gives rise to new neurons but some proliferative VZ cells and/or their progeny, identified by [3H]-thymidine labeling, co-labeled with anti-TR antibody. Acute T4 treatment dramatically increased the number of pyknotic and TUNEL-positive cells in HVC and other telencephalic regions. In contrast, degenerating cells were never observed in the archistriatum or sub-telencephalic regions, suggesting that excess T4 augments cell death selectively in regions that show naturally occurring neuronal turnover. VZ mitotic activity was not altered shortly after acute T4 treatment at a dosage that stimulated cell death, although [3H]-labeling intensity per cell was slightly reduced. Moreover, the incorporation rates for neurons formed shortly before or after acute hormone treatment were no different from control values. Chronic T4 treatment resulted in a reduction in the total number of HVC neurons. Thus, hyperthyroidism augmented neuronal death, which was not compensated for by neuronal replacement. Collectively, these results indicate that excess T4 affects adult neuronal turnover in birds, and raises the possibility that thyroxine plays an important role in the postnatal development of the avian brain and vocal behavior.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76788824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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