A. Bhattacharyya, F. L. Watson, S. Pomeroy, Yan-zhen Zhang, C. Stiles, R. Segal
Target-derived neurotrophins signal from nerve endings to the cell body to influence cellular and nuclear responses. The retrograde signal is conveyed by neurotrophin receptors (Trks) themselves. To accomplish this, activated Trks may physically relocalize from nerve endings to the cell bodies. However, alternative signaling mechanisms may also be used. To identify the vehicle wherein the activated Trks are located and transported, and to identify associated motor proteins that would facilitate transport, we use activation-state specific antibodies in concert with immunoelectron microscopy and deconvolution microscopy. We show that the'activated Trks within rat sciatic nerve axons are preferentially localized to coated and uncoated vesicles. These vesicles are moving in a retrograde direction and so accumulate distal to a ligation site. The P-Trk containing vesicles, in turn, colocalize with dynein components, and not with kinesins. Collectively, these results indicate activated Trk within axons travel in vesicles and dynein is the motor that drives these vesicles towards the cell bodies.
{"title":"High-resolution imaging demonstrates dynein-based vesicular transport of activated Trk receptors.","authors":"A. Bhattacharyya, F. L. Watson, S. Pomeroy, Yan-zhen Zhang, C. Stiles, R. Segal","doi":"10.1002/NEU.10062","DOIUrl":"https://doi.org/10.1002/NEU.10062","url":null,"abstract":"Target-derived neurotrophins signal from nerve endings to the cell body to influence cellular and nuclear responses. The retrograde signal is conveyed by neurotrophin receptors (Trks) themselves. To accomplish this, activated Trks may physically relocalize from nerve endings to the cell bodies. However, alternative signaling mechanisms may also be used. To identify the vehicle wherein the activated Trks are located and transported, and to identify associated motor proteins that would facilitate transport, we use activation-state specific antibodies in concert with immunoelectron microscopy and deconvolution microscopy. We show that the'activated Trks within rat sciatic nerve axons are preferentially localized to coated and uncoated vesicles. These vesicles are moving in a retrograde direction and so accumulate distal to a ligation site. The P-Trk containing vesicles, in turn, colocalize with dynein components, and not with kinesins. Collectively, these results indicate activated Trk within axons travel in vesicles and dynein is the motor that drives these vesicles towards the cell bodies.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"14 1","pages":"302-12"},"PeriodicalIF":0.0,"publicationDate":"2002-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87383797","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}
J. Jacob, J. Haspel, Noriko Kane-Goldsmith, M. Grumet
The neural cell adhesion molecule (CAM) L1 is a member of the immunoglobulin superfamily that has been implicated in neuronal adhesion, neurite outgrowth, and axon guidance. The clinical importance of L1 is illustrated by pathological mutations that lead to hydrocephalus, mental retardation, motor defects, and early mortality. The L1 gene is composed of 28 exons, including exons 2 and 27 that are spliced alternatively, and mutations in exon 2 are associated with severe neurological abnormalities in humans. To elucidate the role of L1 exon 2, a recombinant Fc fusion protein called Delta2L1 was constructed lacking the second exon in the extracellular domain of L1. When bound to fluorescent beads, L1 exhibited homophilic binding while Delta2L1 did not. However, L1 beads coaggregated with the Delta2L1 beads. Similarly, in cell binding studies, L1 bound to L1 and Delta2L1 did not bind to Delta2L1 but it bound moderately to L1. Given the reduced binding of Delta2L1, we tested its effect on neurons. By comparison to L1, a lower percentage of dissociated neurons extended neurites on Delta2L1, and there was a modest decrease in the length of the neurites that grew. Neurite outgrowth from reaggregated neurons was much less robust on Delta2L1 than on L1. The combined results indicate that Delta2L1 does not bind homophilically but it can interact with L1 containing exon 2. The reduced binding and neurite promoting activity of Delta2L1 provides an explanation for certain pathological mutations in L1 that lead to clinically apparent disease in the absence of the normal form of L1 in the nervous system.
{"title":"L1 mediated homophilic binding and neurite outgrowth are modulated by alternative splicing of exon 2.","authors":"J. Jacob, J. Haspel, Noriko Kane-Goldsmith, M. Grumet","doi":"10.1002/NEU.10052","DOIUrl":"https://doi.org/10.1002/NEU.10052","url":null,"abstract":"The neural cell adhesion molecule (CAM) L1 is a member of the immunoglobulin superfamily that has been implicated in neuronal adhesion, neurite outgrowth, and axon guidance. The clinical importance of L1 is illustrated by pathological mutations that lead to hydrocephalus, mental retardation, motor defects, and early mortality. The L1 gene is composed of 28 exons, including exons 2 and 27 that are spliced alternatively, and mutations in exon 2 are associated with severe neurological abnormalities in humans. To elucidate the role of L1 exon 2, a recombinant Fc fusion protein called Delta2L1 was constructed lacking the second exon in the extracellular domain of L1. When bound to fluorescent beads, L1 exhibited homophilic binding while Delta2L1 did not. However, L1 beads coaggregated with the Delta2L1 beads. Similarly, in cell binding studies, L1 bound to L1 and Delta2L1 did not bind to Delta2L1 but it bound moderately to L1. Given the reduced binding of Delta2L1, we tested its effect on neurons. By comparison to L1, a lower percentage of dissociated neurons extended neurites on Delta2L1, and there was a modest decrease in the length of the neurites that grew. Neurite outgrowth from reaggregated neurons was much less robust on Delta2L1 than on L1. The combined results indicate that Delta2L1 does not bind homophilically but it can interact with L1 containing exon 2. The reduced binding and neurite promoting activity of Delta2L1 provides an explanation for certain pathological mutations in L1 that lead to clinically apparent disease in the absence of the normal form of L1 in the nervous system.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"17 1","pages":"177-89"},"PeriodicalIF":0.0,"publicationDate":"2002-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78812699","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}
O. Gil, Li Zhang, Suzanne Chen, Y. Ren, A. Pimenta, G. Zanazzi, D. Hillman, P. Levitt, J. Salzer
Neurotrimin (Ntm) and the limbic system-associated membrane protein (LAMP) are members of the IgLON (LAMP, OBCAM, Ntm) family of glycorylphosphatidylinositol anchored neural cell adhesion molecules. We previously reported that LAMP and Ntm promote adhesion and neurite outgrowth via a homophilic mechanism, suggesting that these proteins promote the formation of specific neuronal circuits by homophilic interactions. In this report, we have further characterized the expression and binding specificity of Ntm. Using a newly generated monoclonal antibody to Ntm, we demonstrated that this protein is largely expressed in a complementary pattern to that of LAMP in the nervous system, with co-expression at a few sites. Ntm is expressed at high levels in sensory-motor cortex and, of particular note, is transiently expressed in neurons of cortical barrel fields and corresponding thalamic "barreloids." Binding of a recombinant, soluble form of Ntm to CHO cells expressing either Ntm or LAMP demonstrates that Ntm and LAMP interact both homophilically and heterophilically. In contrast to conventional growth-promoting activity of Ig superfamily members, LAMP strongly inhibits the outgrowth of Ntm-expressing dorsal root ganglion (DRG) neurons in a heterophilic manner. These anatomical and functional data support the concept that homophilic and heterophilic interactions between IgLON family members are likely to play a role in the specification of neuronal projections via growth promoting and inhibiting effects, respectively.
{"title":"Complementary expression and heterophilic interactions between IgLON family members neurotrimin and LAMP.","authors":"O. Gil, Li Zhang, Suzanne Chen, Y. Ren, A. Pimenta, G. Zanazzi, D. Hillman, P. Levitt, J. Salzer","doi":"10.1002/NEU.10050","DOIUrl":"https://doi.org/10.1002/NEU.10050","url":null,"abstract":"Neurotrimin (Ntm) and the limbic system-associated membrane protein (LAMP) are members of the IgLON (LAMP, OBCAM, Ntm) family of glycorylphosphatidylinositol anchored neural cell adhesion molecules. We previously reported that LAMP and Ntm promote adhesion and neurite outgrowth via a homophilic mechanism, suggesting that these proteins promote the formation of specific neuronal circuits by homophilic interactions. In this report, we have further characterized the expression and binding specificity of Ntm. Using a newly generated monoclonal antibody to Ntm, we demonstrated that this protein is largely expressed in a complementary pattern to that of LAMP in the nervous system, with co-expression at a few sites. Ntm is expressed at high levels in sensory-motor cortex and, of particular note, is transiently expressed in neurons of cortical barrel fields and corresponding thalamic \"barreloids.\" Binding of a recombinant, soluble form of Ntm to CHO cells expressing either Ntm or LAMP demonstrates that Ntm and LAMP interact both homophilically and heterophilically. In contrast to conventional growth-promoting activity of Ig superfamily members, LAMP strongly inhibits the outgrowth of Ntm-expressing dorsal root ganglion (DRG) neurons in a heterophilic manner. These anatomical and functional data support the concept that homophilic and heterophilic interactions between IgLON family members are likely to play a role in the specification of neuronal projections via growth promoting and inhibiting effects, respectively.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"12 1","pages":"190-204"},"PeriodicalIF":0.0,"publicationDate":"2002-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81952016","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}
H. Hirase, Volodymyr Nikolenko, J. Goldberg, R. Yuste
We pulsed the activation of neurons using a femtosecond laser. Pyramidal neurons are depolarized and fire action potentials when high intensity mode-locked infrared light irradiates somatic membranes and axon initial segments. This depolarization is reversible, does not occur with CW laser light, and appears to be due to multiphoton excitation. We describe two regimes of multiphoton optical stimulation. Low intensity, long duration laser irradiation produces a sustained depolarization, insensitive to sodium channel blockers yet sensitive to antioxidants. On the other hand, high intensity, short duration irradiation can induce fast depolarizations, which appear due to different mechanism. The combination of multiphoton stimulation and optical probing could enable systematic analysis of circuits.
{"title":"Multiphoton stimulation of neurons.","authors":"H. Hirase, Volodymyr Nikolenko, J. Goldberg, R. Yuste","doi":"10.1002/NEU.10056","DOIUrl":"https://doi.org/10.1002/NEU.10056","url":null,"abstract":"We pulsed the activation of neurons using a femtosecond laser. Pyramidal neurons are depolarized and fire action potentials when high intensity mode-locked infrared light irradiates somatic membranes and axon initial segments. This depolarization is reversible, does not occur with CW laser light, and appears to be due to multiphoton excitation. We describe two regimes of multiphoton optical stimulation. Low intensity, long duration laser irradiation produces a sustained depolarization, insensitive to sodium channel blockers yet sensitive to antioxidants. On the other hand, high intensity, short duration irradiation can induce fast depolarizations, which appear due to different mechanism. The combination of multiphoton stimulation and optical probing could enable systematic analysis of circuits.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"287 1","pages":"237-47"},"PeriodicalIF":0.0,"publicationDate":"2002-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74985605","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}
Michael W Shiflett, K. Gould, T. Smulders, T. Devoogd
The hippocampal formation (HF) of food-storing birds is larger than non-storing species, and the size of the HF in food-storing Black-Capped Chickadees (Poecile atricapillus) varies seasonally. We examined whether the volume of the septum, a medial forebrain structure that shares reciprocal connections with the HF, demonstrates the same species and seasonal variation as has been shown in the HF. We compared septum volume in three parid species; non-storing Blue Tits (Parus caeruleus) and Great Tits (Parus major), and food-storing Black-Capped Chickadees. We found the relative septum volume to be larger in chickadees than in the non-storing species. We also compared septum and nucleus of the diagonal band (NDB) volume of Black-Capped Chickadees at different times of the year. We found that the relative septum volume varies seasonally in food-storing birds. The volume of the NDB does not vary seasonally. Due to the observed species and seasonal variation, the septum, like the hippocampal formation of food-storing birds, may be specialized for some aspects of food-storing and spatial memory.
{"title":"Septum volume and food-storing behavior are related in parids.","authors":"Michael W Shiflett, K. Gould, T. Smulders, T. Devoogd","doi":"10.1002/NEU.10054","DOIUrl":"https://doi.org/10.1002/NEU.10054","url":null,"abstract":"The hippocampal formation (HF) of food-storing birds is larger than non-storing species, and the size of the HF in food-storing Black-Capped Chickadees (Poecile atricapillus) varies seasonally. We examined whether the volume of the septum, a medial forebrain structure that shares reciprocal connections with the HF, demonstrates the same species and seasonal variation as has been shown in the HF. We compared septum volume in three parid species; non-storing Blue Tits (Parus caeruleus) and Great Tits (Parus major), and food-storing Black-Capped Chickadees. We found the relative septum volume to be larger in chickadees than in the non-storing species. We also compared septum and nucleus of the diagonal band (NDB) volume of Black-Capped Chickadees at different times of the year. We found that the relative septum volume varies seasonally in food-storing birds. The volume of the NDB does not vary seasonally. Due to the observed species and seasonal variation, the septum, like the hippocampal formation of food-storing birds, may be specialized for some aspects of food-storing and spatial memory.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"3 1","pages":"215-22"},"PeriodicalIF":0.0,"publicationDate":"2002-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86646491","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}
T. Umemiya, Etsuko Takasu, M. Takeichi, T. Aigaki, A. Nose
The Drosophila neuromuscular connectivity provides an excellent model system for studies on target recognition and selective synapse formation. To identify molecules involved in neuromuscular recognition, we conducted gain-of-function screening for genes whose forced expression in all muscles alters the target specificity. We report here the identification of a novel transmembrane protein, Forked end (FEND), encoded by the fend gene, by the said screening. When the FEND expression was induced in all muscles, motoneurons that normally innervate muscle 12 formed ectopic synapses on a neighboring muscle 13. The target specificity of these motoneurons was also altered in the loss-of-function mutant of fend. During embryonic development, fend mRNA was detected in a subset of cells in the central nervous system and in the periphery. These results suggest that FEND is a novel axon guidance molecule involved in neuromuscular specificity.
{"title":"Forked end: a novel transmembrane protein involved in neuromuscular specificity in drosophila identified by gain-of-function screening.","authors":"T. Umemiya, Etsuko Takasu, M. Takeichi, T. Aigaki, A. Nose","doi":"10.1002/NEU.10063","DOIUrl":"https://doi.org/10.1002/NEU.10063","url":null,"abstract":"The Drosophila neuromuscular connectivity provides an excellent model system for studies on target recognition and selective synapse formation. To identify molecules involved in neuromuscular recognition, we conducted gain-of-function screening for genes whose forced expression in all muscles alters the target specificity. We report here the identification of a novel transmembrane protein, Forked end (FEND), encoded by the fend gene, by the said screening. When the FEND expression was induced in all muscles, motoneurons that normally innervate muscle 12 formed ectopic synapses on a neighboring muscle 13. The target specificity of these motoneurons was also altered in the loss-of-function mutant of fend. During embryonic development, fend mRNA was detected in a subset of cells in the central nervous system and in the periphery. These results suggest that FEND is a novel axon guidance molecule involved in neuromuscular specificity.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"22 1","pages":"205-14"},"PeriodicalIF":0.0,"publicationDate":"2002-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84993845","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.-K. Park, S. Shanbhag, A. Dubin, M. de Bruyne, Q. Wang, P. Yu, N. Shimoni, S. D'Mello, J. Carlson, G. L. Harris, R. Steinbrecht, C. Pikielny
The olfactory organs on the head of Drosophila, antennae and maxillary palps, contain several hundred olfactory hairs, each with one or more olfactory receptor neurons. Olfactory hairs belong to one of three main morphological types, trichoid, basiconic, and coeloconic sensilla, and show characteristic spatial distribution patterns on the surface of the antenna and maxillary palps. Here we show that targeting expression of the cell-death gene reaper to basiconic sensilla (BS) causes the specific inactivation of most olfactory sensilla of this type with no detectable effect on other types of olfactory sensilla or the structure of the antennal lobe. Our data suggest that BS are required for a normal sensitivity to many odorants with a variety of chemical structures, through a wide range of concentrations. Interestingly, however, in contrast to other odorants tested, the behavioral response of ablated flies to intermediate concentrations of propionic and butyric acids is normal, suggesting the involvement of sensilla unaffected by ectopic reaper expression, probably coeloconic sensilla that respond strongly to these two organic acids. As inactivation of BS causes an underestimation of the concentration of both acids detectable at both the highest and lowest odorants concentrations, our results suggest that concentration coding for these two odorants relies on the integration of signals from different subsets of sensilla, most likely of different morphological types.
{"title":"Inactivation of olfactory sensilla of a single morphological type differentially affects the response of Drosophila to odors.","authors":"S.-K. Park, S. Shanbhag, A. Dubin, M. de Bruyne, Q. Wang, P. Yu, N. Shimoni, S. D'Mello, J. Carlson, G. L. Harris, R. Steinbrecht, C. Pikielny","doi":"10.1002/NEU.10057","DOIUrl":"https://doi.org/10.1002/NEU.10057","url":null,"abstract":"The olfactory organs on the head of Drosophila, antennae and maxillary palps, contain several hundred olfactory hairs, each with one or more olfactory receptor neurons. Olfactory hairs belong to one of three main morphological types, trichoid, basiconic, and coeloconic sensilla, and show characteristic spatial distribution patterns on the surface of the antenna and maxillary palps. Here we show that targeting expression of the cell-death gene reaper to basiconic sensilla (BS) causes the specific inactivation of most olfactory sensilla of this type with no detectable effect on other types of olfactory sensilla or the structure of the antennal lobe. Our data suggest that BS are required for a normal sensitivity to many odorants with a variety of chemical structures, through a wide range of concentrations. Interestingly, however, in contrast to other odorants tested, the behavioral response of ablated flies to intermediate concentrations of propionic and butyric acids is normal, suggesting the involvement of sensilla unaffected by ectopic reaper expression, probably coeloconic sensilla that respond strongly to these two organic acids. As inactivation of BS causes an underestimation of the concentration of both acids detectable at both the highest and lowest odorants concentrations, our results suggest that concentration coding for these two odorants relies on the integration of signals from different subsets of sensilla, most likely of different morphological types.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"18 1","pages":"248-60"},"PeriodicalIF":0.0,"publicationDate":"2002-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88992148","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}
Earlier reports suggested that seasonal variation in food-caching behavior (caching intensity and cache retrieval accuracy) might correlate with morphological changes in the hippocampal formation, a brain structure thought to play a role in remembering cache locations. We demonstrated that changes in cache retrieval accuracy can also be triggered by experimental variation in food supply: captive mountain chickadees (Poecile gambeli) maintained on limited and unpredictable food supply were more accurate at recovering their caches and performed better on spatial memory tests than birds maintained on ad libitum food. In this study, we investigated whether these two treatment groups also differed in the volume and neuron number of the hippocampal formation. If variation in memory for food caches correlates with hippocampal size, then our birds with enhanced cache recovery and spatial memory performance should have larger hippocampal volumes and total neuron numbers. Contrary to this prediction we found no significant differences in volume or total neuron number of the hippocampal formation between the two treatment groups. Our results therefore indicate that changes in food-caching behavior and spatial memory performance, as mediated by experimental variations in food supply, are not necessarily accompanied by morphological changes in volume or neuron number of the hippocampal formation in fully developed, experienced food-caching birds.
{"title":"Changes in spatial memory mediated by experimental variation in food supply do not affect hippocampal anatomy in mountain chickadees (Poecile gambeli).","authors":"V. Pravosudov, Pierre Lavenex, N. S. Clayton","doi":"10.1002/NEU.10045","DOIUrl":"https://doi.org/10.1002/NEU.10045","url":null,"abstract":"Earlier reports suggested that seasonal variation in food-caching behavior (caching intensity and cache retrieval accuracy) might correlate with morphological changes in the hippocampal formation, a brain structure thought to play a role in remembering cache locations. We demonstrated that changes in cache retrieval accuracy can also be triggered by experimental variation in food supply: captive mountain chickadees (Poecile gambeli) maintained on limited and unpredictable food supply were more accurate at recovering their caches and performed better on spatial memory tests than birds maintained on ad libitum food. In this study, we investigated whether these two treatment groups also differed in the volume and neuron number of the hippocampal formation. If variation in memory for food caches correlates with hippocampal size, then our birds with enhanced cache recovery and spatial memory performance should have larger hippocampal volumes and total neuron numbers. Contrary to this prediction we found no significant differences in volume or total neuron number of the hippocampal formation between the two treatment groups. Our results therefore indicate that changes in food-caching behavior and spatial memory performance, as mediated by experimental variations in food supply, are not necessarily accompanied by morphological changes in volume or neuron number of the hippocampal formation in fully developed, experienced food-caching birds.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"57 1","pages":"142-8"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84719930","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 embryo, axon growth and guidance depend on cues that include diffusible molecules. We have shown previously that the branchial arches and hepatocyte growth factor (HGF) are growth-promoting and chemoattractant for young embryonic cranial motor axons. HGF is produced in the branchial arches of the embryo, but a number of lines of evidence suggest that HGF is unlikely to be the only factor involved in the growth and guidance of these axons. Here we investigate whether other neurotrophic factors could be involved in the growth of young cranial motor neurons in explant cultures. We find that brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and cardiotrophin-1 (CT-1) all promote the outgrowth of embryonic cranial motor neurons, while glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) fail to affect outgrowth. We next examined whether HGF and the branchial arches had similar effects on motor neuron subpopulations at different axial levels. Our results show that HGF acts as a generalized rather than a specific neurotrophic factor and guidance cue for cranial motor neurons. Although the branchial arches also had general growth-promoting effects on all motor neuron subpopulations, they chemoattracted different axial levels differentially, with motor neurons from the caudal hindbrain showing the most striking response.
{"title":"Comparison of the effects of HGF, BDNF, CT-1, CNTF, and the branchial arches on the growth of embryonic cranial motor neurons.","authors":"Arifa Naeem, L. Abbas, S. Guthrie","doi":"10.1002/NEU.10048","DOIUrl":"https://doi.org/10.1002/NEU.10048","url":null,"abstract":"In the developing embryo, axon growth and guidance depend on cues that include diffusible molecules. We have shown previously that the branchial arches and hepatocyte growth factor (HGF) are growth-promoting and chemoattractant for young embryonic cranial motor axons. HGF is produced in the branchial arches of the embryo, but a number of lines of evidence suggest that HGF is unlikely to be the only factor involved in the growth and guidance of these axons. Here we investigate whether other neurotrophic factors could be involved in the growth of young cranial motor neurons in explant cultures. We find that brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and cardiotrophin-1 (CT-1) all promote the outgrowth of embryonic cranial motor neurons, while glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) fail to affect outgrowth. We next examined whether HGF and the branchial arches had similar effects on motor neuron subpopulations at different axial levels. Our results show that HGF acts as a generalized rather than a specific neurotrophic factor and guidance cue for cranial motor neurons. Although the branchial arches also had general growth-promoting effects on all motor neuron subpopulations, they chemoattracted different axial levels differentially, with motor neurons from the caudal hindbrain showing the most striking response.","PeriodicalId":16540,"journal":{"name":"Journal of neurobiology","volume":"36 1","pages":"101-14"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85441144","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}
J. Heinrich, T. D. Singh, F. Sohrabji, K. Nordeen, E. Nordeen
Developmental changes in the composition of NMDA receptors can alter receptor physiology as well as intracellular signal transduction cascades, potentially shifting thresholds for neural and behavioral plasticity. During song learning in zebra finches, NMDAR currents become faster, and transcripts for the modulatory NR2B subunit of this receptor decrease in lMAN, a region in which NMDAR activation is critical for vocal learning. Using in situ hybridization, we found that NR2A transcripts change reciprocally, increasing significantly in both lMAN (59%) and in another song region, Area X (38%), between posthatch day (PHD) 20 and 40, but not changing further at PHD60 or 80. In adjacent areas not associated with song learning, NR2A mRNA did not change between PHD20-80. Although early song deprivation (which extends the sensitive period for song learning) delays changes in NR2B gene expression and NMDAR physiology within the lMAN, it did not alter NR2A mRNA levels measured at PHD40, 45, or 60. Early testosterone (T) treatment, which disrupts vocal development and accelerates the maturation of both NR2B levels and NMDAR physiology in lMAN, also significantly increased NR2A transcripts measured at PHD35 in lMAN. In Area X, a similar effect of T approached significance. Together with our previous studies, these results show that in a pathway critical for vocal plasticity, the ratio of NR2A:NR2B mRNA rises abruptly early during the sensitive period for song learning. Furthermore, androgen regulation of NMDAR gene expression may alter thresholds for experience-dependent synaptic change.
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