bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a protein synthesis inhibitor on the hormonally mediated regression and death of motoneurons in the tobacco hornworm, Manduca sexta
Authors: Weeks Janis C. , Davidson Seana K. , Debu Bettina H. G.
Published: January 2005

The larval–pupal transformation of Manduca sexta is accompanied by the loss of the abdominal prolegs. The proleg muscles degenerate, the dendritic arbors of proleg motoneurons regress, and a subset of the proleg motoneurons dies. The regression and death of proleg motoneurons are triggered by the prepupal peak of ecdysteroids in the hemolymph. To investigate the possible involvement of protein synthesis in these events, we gave insects repeated injections of the protein synthesis inhibitor, cycloheximide (CHX), during the prepupal peak. Examination of insects 3–5 days following CHX treatment showed that CHX inhibited the death of proleg motoneurons and the production of pupal cuticle in a dose‐dependent fashion. When insects were allowed to survive for 10 days after the final CHX injection, motoneuron death and pupal cuticle production sometimes occurred belatedly, apparently in response to the ecdysteroid rise that normally triggers adult development. CHX treatments that inhibited motoneuron death were less effective in inhibiting dendritic regression in the same neurons. In another set of experiments, abdomens were isolated from the ecdysteroid‐secreting glands prior to the prepupal peak, and infused with 20‐hydroxyecdysone (20‐HE). Single injections of CHX delivered just prior to the start of the 20‐HE infusion inhibited motoneuron death and pupal cuticle production, but in the range of doses tested, did not prevent dendritic regression. Our findings suggest that protein synthesis is a required step in the steroid‐mediated death of proleg motoneurons, and that dendritic regression is less susceptible to inhibition by CHX than is motoneuron death. © 1993 John Wiley & Sons, Inc.
Distribution of pluripotent neural crest cells in the embryo and the role of brain‐derived neurotrophic factor in the commitment to the primary sensory neuron lineage
Authors: Sieber‐Blum Maya , Ito Kazuo , Richardson Michael K. , Langtimm Carol J. , Duff R. Scott
Published: January 2005

Many early migratory neural crest cells are pluripotent in the sense that their progeny are able to generate more than one differentiated phenotype (Sieber‐Blum and Cohen, 1980, Dev. Biol. 80:95–106; Baroffio, Dupin, and Le Douarin, 1988, Proc. Natl. Acad. Sci. USA 85:5325–5329; Bronner‐Fraser and Fraser, 1988, Nature 335:161–164; Sieber‐Blum, 1989a, Science 243:1608–1611; Ito and Sieber‐Blum, 1991, Dev. Biol. 148:95–106). At trunk levels, the neural crest contains two classes (Sieber‐Blum and Cohen, 1980) and at posterior rhombencephalic levels, three different classes of pluripotent cells (Ito and Sieber‐Blum, 1991). We investigated cell differentiation by in vitro clonal analysis to determine when in development the pool of pluripotent neural crest cells becomes exhausted. The data suggest that different classes of pluripotent cells, precursor cells with more restricted developmental potentials, and apparently committed cells, exist at sites of advanced migration (posterior branchial arches) and even at target sites of neural crest cell differentiation [posterior branchial arches, dorsal root ganglia (DRG), sympathetic ganglia (SG), and epidermal ectoderm]. Some putative classes of pluripotent cells persist well into the second half of embryonic development. These observations have implications for our understanding of the mechanisms that control neural crest cell migration and differentiation. They support the idea that cues originating from the microenvironment affect differentiation of pluripotent neural crest cells. One such signal appears to be brain‐derived neurotrophic factor (BDNF). In the presence of BDNF, but not nerve growth factor (NGF), there is a significant increase in the number of neural crest cells per colony that express a sensory neuron‐specific marker. Because this increase is not accompanied by a corresponding increase in the total number of cells per colony, this suggests that BDNF plays a role in cell type specification. © 1993 John Wiley & Sons, Inc.
Cell interactions that determine sympathetic neuron transmitter phenotype and the neurokines that mediate them
Authors: Rao M. S. , Landis S. C.
Published: January 2005

The transmitter properties of both developing and mature sympathetic neurons are plastic and can be modulated by a number of environmental cues. Cell culture studies demonstrate that noradrenergic neurons can be induced to become cholinergic and that the expression of neuropeptides can be altered. Similar changes in transmitter phenotype occur in vivo. During development, noradrenergic neurons that innervate eccrine sweat glands acquire cholinergic and peptidergic function. This change is dependent upon interactions with the target tissue. Following injury of sympathetic neurons in developing and adult animals, striking alterations take place in peptide expression. Ciliary neurotrophic factor and cholinergic differentiation factor/leukemia inhibitory factor, members of a family that includes several hematopoeitic cytokines, induce cholinergic function and modulate neuropeptide expression in cultured sympathetic neurons. Studies in progress provide evidence that members of this new cytokine family influence the transmitter phenotype of sympathetic neurons not only in vitro but also in vivo. © 1993 John Wiley & Sons, Inc.
Spatial integration among cells forming the cranial peripheral nervous system
Authors: Noden Drew M.
Published: January 2005

Neural crest cells represent a unique link between axial and peripheral regions of the developing vertebrate head. Although their fates are well catalogued, the issue of their role in spatial organization is less certain. Recent data, particularly on patterns of expression of Hox genes in the hindbrain and crest cells, have raised anew the debate whether a segmental arrangement is the basis for positional specification of craniofacial epithelial and mesenchymal tissues or is but one manifestation of underlying spatial programming processes. The mechanisms of positional specification of sensory neurons derived from the neural crest and placodes are unknown. This review examines the spatial organization of cells and tissues that develop in proximity to sensory neurons; some of these tissues share a common ancestry, others are targets of cranial sensory and motor nerves. All share the necessity of acquiring and expressing site‐specific properties in a functionally integrated manner. This integration occurs in part by coordinating patterns of cell migration, as occurs between migrating crest cells and branchial arch myoblasts. Constant rostro‐caudal relations are maintained among these precursors as they move dorsoventrally from the hindbrain–paraxial regions to establish branchial arches. During this period the interactions among these and other mesenchymal cells are hierarchical; each cell population differentially integrates its past with cues emanating from new microenvironments. Analyses of tissue interactions indicate that neural crest cells play a dominant role in this scenario. © 1993 John Wiley & Sons, Inc.
Antiserum to an eye‐specific protein identifies photoreceptor and circadian pacemaker neuron projections in Aplysia
Authors: Strack Stefan , Jacklet Jon W.
Published: January 2005

The marine gastropod Aplysia has a circadian clock in each eye that generates a circadian rhythm of optic nerve activity. The axons of pacemaker neurons carry the rhythmic activity to the brain where it can be recorded from various ganglionic connectives as it is distributed throughout the CNS. We had previously identified an eye‐specific 48‐kD protein using an antiserum, anti‐S, that recognizes the period gene product of Drosophila. We have now obtained two partial amino acid sequences of the 48‐kD protein and raised a polyclonal antiserum using a synthetic peptide with the amino acid sequence of one of them. The antiserum recognizes a family of spots of Mr 47–48 kD and Pi 5.9–6.0 on 2D immunoblots of eye proteins. The immunoblot staining intensity does not exhibit a circadian rhythm. Used in immunocytochemistry, the antiserum recognizes fibers in the optic nerve and retinal neuropil, pacemaker neurons, certain photoreceptors, and the photoreceptor rhabdom layer. It stains the optic nerve fibers and optic fiber terminals in the cerebral optic ganglion and recognizes the cerebral optic tracts, putative synaptic exchange areas, and optic tract projections from the cerebral ganglion into various head nerves and interganglionic connectives. The function of the 48‐kD protein is not known but it could be involved in the maintenance or regulation of the retinal afferent pathways, including the pacemaker neuron axons, known from previous axonal transport and electrical recording studies to be the circadian output pathway. © 1993 John Wiley & Sons, Inc.
Ecdysteroid regulation of olfactory protein expression in the developing antenna of the tobacco hawk moth, Manduca sexta
Authors: Vogt Richard G. , Rybczynski Robert , Cruz Manuel , Lerner Michael R.
Published: January 2005

During adult metamorphosis, the moth olfactory neurons and their glia‐like support cells pass through a coordinated and synchronous development. By 60% of development, the olfactory system is anatomically complete, but functional maturation does not occur until about 90% of development. Maturation is characterized by the onset of odorant sensitivity in the sensory neurons and the expression of certain antennal‐specific proteins including odorant binding proteins (OBPs) and odorant degrading enzymes (ODEs). The OBPs have been cloned and sequenced, and are thus useful models for investigating the molecular mechanisms coordinating final maturation of the developing olfactory system. The ecdysteroid hormones have been observed to regulate many cellular level neuronal changes during adult metamorphosis. In particular, the late pupal decline in ecdysteroids is known to influence programmed death of nerves and muscles at the end of metamorphoses. Experiments are presented here which indicate that this decline in ecdysteroids also induces the expression of the OBPs. Normal OBP expression occurs 35–40 h before adult emergence. In culture, OBP expression could be induced at least 90 h before adult emergence by the premature removal of ecdysteroid. This premature expression was blocked by culturing tissue in the presence of the biologically active ecdysteroid 20‐hydroxyecdysone. These findings suggest that maturation of the olfactory system is regulated by the decline in ecdysteroids, and support the view that olfactory development, in general, may be coordinated by chaging levels of pupal ecdysteroids. © 1993 John Wiley & Sons, Inc.
Establishment of vagal sensorimotor circuits during fetal development in rats
Authors: Rinaman Linda , Levitt Pat
Published: January 2005

The differentiation of vagal motor neurons and their emerging central relationship with vagal sensory afferents was examined in fetal rats. To identify peripherally projecting sensory and motor neurons, 1,1′‐dioctadecyl 3,3,3′,3′‐tetramethylindocarbocyanine perchloarate (DiI) was inserted into the proximal gut or cervical vagus nerve in fixed preparations. At embryonic day (E) 12, labeled vagal sensory neurons are present in the nodose ganglia and a few sensory axons project into the dorsolateral medulla. Central sensory processes become increasingly prevalent between E13 and E14 but remain restricted to the solitary tract. Vagal motor neurons are first labeled at E13, clustered within a region corresponding to the nucleus ambiguus (NA). Additional motor neurons appear to be migrating toward the NA from the germinal zone of the fourth ventricle. Motor neurons in the dorsal motor nucleus of the vagus (DMV) first project to the gut at E14 and have processes that remain in physical contact with the ventricular zone through E16. Sensory axons emerge from the solitary tract at E15 and project medially through the region of the nucleus of the solitary tract (NST) to end in the ventricular zone. A possible substrate for direct vagovagal, sensorimotor interaction appears at E16, when vagal sensory fibers arborize within the DMV and DMV dendrites extend into the NST. By E18, the vagal nuclei appear remarkably mature. These data suggest specific and discrete targeting of vagal sensory afferents and motor neuron dendrites in fetal rats and define an orderly sequence of developmental events that precedes the establishment of vagal sensorimotor circuits. © 1993 John Wiley & Sons, Inc.
Bromodeoxyuridine labeling reveals a class of satellite‐Like cells within the electric organ
Authors: Patterson John M. , Zakon Harold H.
Published: January 2005

When the electric organ (EO) of weakly electric fish is amputated, a blastema forms from which new EO and muscle cells arise. However, the progenitor cells that contribute to the blastema are unknown. We studied regeneration of the electric organ in Sternopygus to answer this question. The EO of this species is composed of electrocyte cells surrounded by peripheral bundles of muscle fibers. Fish were injected with 5′‐bromodeoxyuridine (BrdU) 24 h after amputating the terminal portion of the EO. At this time, a population of small cells were labeled in the extracellular matrix between electrocytes and muscle fibers. These cells did not label in control fish injected with saline or in nonamputated BrdU‐injected fish. For the first 6 days postamputation, increasing numbers of BrdU‐labeled cells appeared at the wound margin. A blastema formed 6 days after amputation and contained numerous BrdU‐labeled cells. At 10 days postamputation, clusters of BrdU‐positive cells were seen throughout the wound margin and proximal blastema. At 14 days, BrdU‐labeled nuclei were present within developing electrocytes. Labeling alternate sections with MF20 antimyosin and AE1 anticytokeratin antibodies confirmed that BrdU‐positive multinucleate cells coexpress myosin and cytokeratin epitopes, diagnostic of newly regenerated electrocytes. Electron micrographs reveal that the small cells surrounding muscles and electrocytes are similar; they contain an elongate nucleus, are largely devoid of cytoplasm, and possess few organelles. This morphology and evidence of myogenic potential suggests that these cells are satellite cells. © 1993 John Wiley & Sons, Inc.
Neuronal development in the Drosophila retina
Authors: Venkatesh Tadmiri
Published: January 2005

Nervous systems of higher organisms are comprised of a variety of cell types which are interconnected in a precise manner. The molecular mechanisms that lead to the specification of neuronal cell types are not well understood. The compound eye of the fruit fly Drosophila is an attractive experimental system to understand these mechanism. The compound eye is a reiterated neural pattern with several hundred unit structures and is amenable to both classical and molecular genetic methods. During the development of the compound eye cell–cell interactions and positional information play a critical role in the determination of cell fate. Recent genetic and molecular studies have provided important clues regarding the nature of the molecules involved in cellular signalling and neuronal differentiation. © 1993 John Wiley & Sons, Inc.
Natural fluctuation and gonadal hormone regulation of astrocyte immunoreactivity in dentate gyrus
Authors: Luquin Sonia , Naftolin Frederick , Garcia‐Segura Luis Miguel
Published: January 2005

The 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 Wiley & Sons, Inc.
Synaptic repression at crayfish neuromuscular junctions. I. Generation after partial target area removal
Authors: Prosser Pamela , Rhee John , Vélez Samuel J.
Published: January 2005

Synaptic 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 Wiley & Sons, Inc.
Glutamate receptor‐mediated currents and toxicity in embryonal carcinoma cells
Authors: Turetsky D. M. , Huettner J. E. , Gottlieb D. I. , Goldberg M. P. , Choi D. W.
Published: January 2005

While primary neuronal cell cultures have been used to investigate excitotoxicity, development of cell lines exhibiting glutamate receptor‐mediated death is desirable. P19 mouse embryonal carcinoma cells, exposed to retinoic acid and plated onto a layer of cultured mouse cortical glial cells, differentiated into neuron‐like elements immunoreactive for neurofilaments and neuron‐specific enolase. Whole‐cell recordings revealed inward currents in response to extracellular application of either NMDA or kainate. The NMDA‐induced currents exhibited a voltage‐dependent blockade by magnesium, required glycine for maximal activation, and were blocked by the NMDA antagonist dizocilpine. Kainate‐induced currents were blocked by the AMPA/kainate receptor antagonist CNQX. Exposure to 500 μM NMDA for 24 h destroyed most P19 cells (EC50 approximately 70 μM); death was prevented by dizocilpine or D‐APV. Exposure to 500 μM kainate also resulted in widespread death reduced by CNQX. Thus differentiated P19 cells exhibited both excitatory amino acid responses and vulnerability to excitotoxicity, characteristic of CNS neurons. These cells may provide a genetically open system useful for studying glutamate receptor‐mediated phenomena at a molecular level. © 1993 John Wiley & Sons, Inc.
Effects of the steroid hormone 20‐hydroxyecdysone and prior sensory input on the survival and growth of moth central olfactory neurons in vitro
Authors: Oland Lynne A. , Hayashi Jon H.
Published: January 2005

Neurons in the developing (antennal) olfactory lobe of the moth Manduca sexta undergo a period of extensive process outgrowth and branching that coincides temporally with both a rising titer of the steroid hormone 20‐hydroxyecdysone and the ingrowth of sensory axons from receptors in the antenna. To evaluate the contribution of these two influences to the morphological development of antennal‐lobe neurons, we placed the neurons in cell culture. Antennal‐lobe neurons were dissociated from normal and chronically unafferented lobes at different stages of development and were exposed to different doses of hormone. Six neuronal cell types with distinctive and stable morphologies appeared in cultures from all stages of pupal development. Morphological changes in these neuronal types were examined quantitatively by comparison of the total length and number of branches. We found that 20‐hydroxyecdysone had little direct effect on the morphological development of antennal‐lobe neurons, but brief exposure to sensory axons in vivo prior to dissociation significantly enhanced subsequent outgrowth in culture. © 1993 John Wiley & Sons, Inc.
Transplantation of neurons reveals processing areas and rules for synaptic connectivity in the cricket nervous system
Authors: Killian K. A. , Merritt D. J. , Murphey R. K.
Published: January 2005

In order to assess the nature of spatial cues in determining the characteristic projection sites of sensory neurons in the CNS, we have transplanted sensory neurons of the cricket Acheta domesticus to ectopic locations. Thoracic campaniform sensilla (CS) function as proprioceptors and project to an intermediate layer of neuropil in thoracic ganglia while cercal CS transduce tactile information and project into a ventral layer in the terminal abdominal ganglion (TAG). When transplanted to ectopic locations, these afferents retain their modality‐specific projection in the host ganglion and terminate in the layer of neuropil homologous to that of their ganglion of origin. Thus, thoracic CS neurons project to intermediate neuropil when transplanted to the abdomen and cercal CS neurons project to a ventral layer of neuropil when transplanted to the thorax. We conclude that CS can be separated into two classes based on their characteristic axonal projections within each segmental ganglion. We also found that the sensory neurons innervating tactile hairs project to ventral neuropil in any ganglion they encounter after transplantation. Ectopic sensory neurons can form functional synaptic connections with identified interneurons located within the host ganglia. The new contacts formed by these ectopic sensory neurons can be with normal targets, which arborize within the same layer of neuropil in each segmental ganglion, or with novel targets, which lack dendrites in the normal ganglion and are thus normally unavailable for synaptogenesis. These observations suggest that a limited set of molecular markers are utilized for cell–cell recognition in each segmentally homologous ganglion. Regenerating sensory neurons can recognize novel postsynaptic neurons if they have dendrites in the appropriate layer of neuropil. We suggest that spatial constraints produced by the segmentation and the modality‐specific layering of the nervous system have a pivotal role in determining synaptic specificity. © 1993 John Wiley & Sons, Inc.
Hoxhomeobox genes and regionalisation of the nervous system
Authors: Krumlauf Robb , Marshall Heather , Studer Michéle , Nonchev Stefan , Sham Mai Har , Lumsden Andrew
Published: January 2005

TheHoxfamily of homeobox‐containing genes are intimately associated with the processes of axial patterning in vertebrate embryos. This family of transcription factors is widely conserved in evolution and by analogy with theirDrosophilacounterparts, theHOM‐Chomeotic genes, may play a role in establishing regional identity in a number of embryonic systems, including the CNS. The patterns of expression of these genes are linked with the generation of rhombomeres and neural crest in the developing hindbrain, and suggest that they provide a molecular system for generating a combinatorial patterning mechanism. Analysis of mouseHoxmutants generated by homologous recombination have clearly demonstrated that the genes have important roles in normal regionalisation of the hindbrain and branchial arches, and this has lead to interest in how their early patterns are established in the nervous system. TheHoxgenes and their relation to hindbrain segmentation therefore provide a means of examining the cascade of events which regulates pattern formation in early neural development. © 1993 John Wiley & Sons, Inc.
Antennapedia‐Class homeobox genes define diverse neuronal sets in the embryonic CNS of the leech
Authors: Aisemberg Gabriel O. , Wysocka‐Diller Joanna , Wong Victoria Y. , Macagno Eduardo R.
Published: January 2005

Studies of the Antennapedia‐class homeobox genes suggest that specific combinations of these transcription factors play a role in defining neuronal identities. We examined the expression of these genes in the leech Hirudo medicinalis, an organism well‐suited for neurobiological research at the level of identified neurons. Leeches contain at least as many Antennapedia‐class and related genes as insects do, despite the apparently lower complexity of the leech body plan. The CNS expression patterns of two Antennapedia‐class leech homeobox genes (Lox genes) were examined in detail. Lox1 is expressed during early gangliogenesis in only one pair of transient neurons present in every segment (the Bipolar cells) and, at later stages of embryonic development, in 15–20 pairs of central neurons repeated in most segments. The monoclonal antibody Laz1‐1 identified two pairs of Lox1‐expressing neurons as the Bipolar cells and the L1 neurons. The Bipolar cells extended processes in the primordia of the longitudinal connective nerves and later degenerated. The L1 neurons were detected late in gangliogenesis and became stable neurons. Lox2 is expressed in an iterated set of neurons in the posterior two‐thirds of the CNS. On the basis of cell body position and relative size, two pairs of Lox2‐expressing cells were identified as the RPE‐like neurons and the CV motor neurons. Other Lox genes are also expressed in segmentally repeated subpopulations of neurons. These neuronal subpopulations appear to be different from one another but partially overlapping. Different combinations of Lox genes that may be expressed in individual cells could in theory generate enough variability to specify all central neurons in a leech ganglion. © 1993 John Wiley & Sons, Inc.
Developmental analysis reveals labial and subradular ganglia and the primary framework of the nervous system in nudibranch gastropods
Authors: Page Louise R.
Published: January 2005

Previous ultrastructural observations on late stage larvae of dorid nudibranchs (Gastropoda, Opisthobranchia) revealed two pairs of ganglia within the base of the foot that do not have obvious counterparts in existing descriptions of other gastropod larvae [Chia and Koss (1989). Cell Tiss. Res. 256:17–26.] One of these ganglionic pairs has been implicated in the initiation of settlement preceding metamorphosis [Arkett et al. (1989). Biol. Bull. 176:155–160.] By examining neurogenesis in sequential larval stages, I have found that the pattern of connectives and commissures associated with these enigmatic ganglia is comparable to patterns found in less consolidated adult nervous systems of chitons, monoplacophorans, and archaeogastropods. These comparative date suggest that the two pairs of ganglia in dorid nudibranch larvae are homologues of labial and subradular ganglia. The labial ganglia become incorporated into the cerebral ganglia at metamorphosis. In an attempt to integrate anatomical and developmental observations with behavioral andneurophysiological results, I suggest that receptor cells of the larval labial ganglia may become postmetamorphic primary mechanoreceptors of the oral tube, which have central cell bodies within the “cerebral” ganglia and which help coordinate feeding. Results of this study also address a larger evolutionary issue by questioning the traditional model of an ancestral molluscan nervous system that consists of four longitudinal nerve cords that arise from separate sites along a circumesophageal nerve ring. This pattern results from secondary connections in nudibranchs and possibly other molluscs. The primary condition of a single axon bundle emerging from each cerebral ganglion is more similar to the developing nervous system in polychaete annelids than what has been recognized previously. © 1993 John Wiley & Sons, Inc.
Aspects of early postnatal development of cortical neurons that proceed independently of normally present extrinsic influences
Authors: Annis Casey M. , Robertson Richard T. , O'Dowd Diane K.
Published: January 2005

To examine the contribution of local versus extrinsic influences on postnatal development of cortical neurons, we compared the maturation of deep (infragranular) layer neurons in isolated slices of neocortex grown in organotypic culture to a similar population of neurons developingin vivo. All slice cultures were prepared from sensorimotor cortices of newborn mice (P0) and neurons in these cultures were examined at daily intervals during the first 9 daysin vitro(DIV). The maturational state of neurons developingin vivoover this same time period was assessed in acute slices prepared from animals of equivalent postnatal age, P1–P9. Electrophysiological recordings were obtained from neurons in both cultured and acute slices, using Lucifer yellow filled whole‐cell recording electrodes, enabling subsequent morphometric analysis of the labeled cells. We report significant changes in both cellular morphology and electrical membrane properties of these deep layer cortical neurons during the frist week in culture. Morphological maturation over this time period was characterized by a two‐ to three‐fold increase in cell body size and total process length, and an increase in dendritic complexity. In this same population of cells a three‐fold decrease in input resistance and changes in the action potential waveform, including a two‐fold decrease in the AP duration, also occur. The degree of morphological and electrophysiological differentiation of individual neurons was highly correlated across developmental ages, suggesting that the maturational state of a cell is reflected in both cellular morphology and intrinsic membrane properties. A remarkably similar pattern of neuronal maturation was observed in neurons in layers V, VI/SP examined in acute slices prepared from animals between P1–P9. Because our culture system preserves many aspects of the local cortical environment while eliminating normal extrinsic influences (including thalamic, brainstem, and callosal connections), our findings argue that this early phase of neuronal differentiation, including the rate and extent of dendritic growth and development of AP waveform, results from instructive and/or permissive local influences, and appears to proceed independently of the many normally present extrinsic factors. © 1993 John Wiley & Sons, Inc.
Different forms of 130 kD connective tissue protein are specific for boundaries in the nervous system and basement membrane of muscle cells in leech
Authors: Thorey Irmgard , Zipser Birgit
Published: January 2005

The nervous system and muscle tissue of the leech express two different organ‐specific forms of connective tissue protein. The nervous system‐specific form appears in regional boundaries separating cell bodies, axonal tracts and areas of the neuropile during late embryogenesis. In contrast, the muscle‐specific form appears earlier during development in the basement membrane of muscle cells. In extraction experiments both forms behave like extracellular matrix proteins and because of their molecular weight, are considered members of a group of cell type‐specific 130 kD proteins (leech gp130s). How ever, the two forms differ in their posttranslational modification. As determined by Con A and lentil lectin affinity chromatography, only the nervous system‐specific, but not the muscle‐specific form, has fucosylated and high mannose N‐linked carbohydrates. These differences in the developmental onset and glycosylation suggest that nervous system‐specific and muscle‐specific connective tissue proteins are regulated differently and participate in different molecular interactions. © 1993 John Wiley & Sons, Inc.
Sexually dimorphic neuron number in lumbosacral dorsal root ganglia of the rat: Development and steroid regulation
Authors: Mills Alice C. , Sengelaub Dale R.
Published: January 2005

Rats possess a sexually dimorphic neuromuscular system that controls penile reflexes critical for copulation. This system includes two motor nuclei in the lumbar cord and their target musculature in the perineum. The spinal nucleus of the bulbocavernosus (SNB) and the dorsolateral nucleus (DLN) motoneuron populations and their target perineal muscles are much larger in males than in females. The sex difference in motoneuron number develops via androgen‐regulated differential cell death during the perinatal period; androgen also regulates retention of the target muscles. The developmental pattern and steroid sensitivity of peripheral afferents to the SNB/DLN motor nuclei were previously unknown. In order to characterize the peripheral sensory component of the dimorphic SNB/DLN system, the neurons of the relevant dorsal root ganglia (DRGs) were quantified in terms of number, size, and androgen sensitivity at various perinatal ages. DRG neuron number is greatest prenatally, then decreases in both sexes after birth; the timing and pattern of neuron number development are similar to those seen in the SNB and DLN. Postnatally, males have more DRG neurons than females, as a result of greater neuron death in the DRGs of females. Females treated with testosterone propionate during the perinatal period exhibit masculine development of DRG neuron number. Thus, the normal development of DRG neuron number parallels that of the SNB/DLN motor nuclei and target muscles in pattern and timing, is sexually dimorphic, and is regulated by androgen. © 1993 John Wiley & Sons, Inc.
Changing synaptic specificities in the nervous system of Caenorhabditis elegans: Differentiation of the DD motoneurons
Authors: Walthall W. W. , Li Lei , Plunkett Jeffery A. , Hsu Chia‐Yu
Published: January 2005

During postembryonic development, the DD motoneurons in the nematode Caenorhabditis elegans completely reorganize their pattern of synapses. Ablation of a pair of embryonic precursors results in the absence of this entire class of motoneurons. In their absence animals exhibit two developmentally distinct locomotory defects. The transition period from one defect to the other is correlated with the synaptic reorganization of the DD mns. Mutations in a gene (unc‐123) have been isolated that exhibit locomotory defects similar to those of the ablated adult animals. Genetic and cellular analyses of one of these alleles suggest that the unc‐123 gene product may be involved in the reestablishment of functional synapses in these neurons. © 1993 John Wiley & Sons, Inc.
Inhibitory effects of actinomycin D and cycloheximide on neuronal death in adult Manduca sexta
Authors: Fahrbach S. E. , Choi M. Kim , Truman J. W.
Published: January 2005

A decline in circulating 20‐hydroxyecdysone permits the emergence of the adult Manduca sexta moth; this endocrine signal also triggers the death of approximately half of the neurons in the unfused abdominal ganglia of the moth central nervous system. This programmed death of neurons was markedly reduced by treatment with either actinomysin D (an RNA synthesis inhibitor) or cycloheximide (a protein synthesis inhibitor). Similar results were found after addition of these agents to ventral nerve cord cultures. The effectiveness of these treatments in delaying or blocking neuronal death depended upon their time of administration relative to the normal time of post‐emergence death in the particular motoneuron under study: late‐dying neurons, for example, could still be saved by these treatments even after early‐dying neurons had already initiated degeneration. In both intact moths and cultured ventral nerve cords, the ability of actinomycin D to prevent neuronal death waned at the same time at which replacement of the steroid hormone could no longer block neuronal death. This suggests that the steroid commitment point represents the time at which the genes that mediate cell death are transcribed. Cycloheximide remained effective in delaying or blocking neuronal death until shortly before the onset of degeneration, suggesting that ongoing protein synthesis is essential for the initiation of the degeneration response. 1994 John Wiley & Sons, Inc.
Substrate‐dependent interactions of leech microglial cells and neurons in culture
Authors: Masuda‐Nakagawa L. M. , Walz A. , Brodbeck D. , Neely M. D. , Grumbacher‐Reinert S.
Published: January 2005

The principal aim of the present experiments has been to analyze the properties of microglial cells and their role in nerve regeneration. In the leech, damage to the CNS has been shown to be followed by accumulation of laminin and microglial cells at the site of injury (Masuda‐Nakagawa et al., 1990. Proc. R. Sco. Lond. B. 241:201–206; and 1993. Proc. Natl. Acad. Sci. USA 90:4966–4970). Procedures were devised for isolating these small, wandering cells from the CNS of the leech. In culture, they were reliably identified by their sizes, shapes, and phagocytotic activity. Their morphology, motility, and interactions with neurons were influenced by the substrate molecules on which they were plated. On the plant lectin concanavalin A (Con A) microglia had a rounded shape and remained stationary. By contrast on extracts of leech extracellular matrix (ECM) enriched with laminin the cells were mobile and spindle‐shaped with long processes. On Con A, neuronal growth cones avoided microglial cells, whereas on ECM extract the presence of a microglial cell did not influence neurite growth. Microglial cells showed immunoreactivity on both substrates when stained with a monoclonal antibody against leech laminin. Together these results suggest that microglial cells are influenced in their properties by molecules in the environment and that they could contribute to neuronal outgrowth at the site of any injury. 1994 John Wiley & Sons, Inc.
Regulation of immediate‐early gene expression in rat retinal ganglion cells after axotomy and during regeneration through a peripheral nerve graft
Authors: Hüll Michael , Bähr Mathias
Published: January 2005

To determine mechanisms of structural plasticity in adult CNS neurons, we investigated the expression of immediate early genes (IEGs) in the rat retina. Gene products of different IEG families (JUN and FOS proteins) and cAMP‐responsive element binding protein (CREBP) were examined by immunohistochemistry under three different paradigms. Normal rats which were not axotomized were compared with axotomized animals, where retinal ganglion cells (RGCs) were axotomized by intraorbital optic nerve cut and retrogradely labeled with fluorogold (FG). Under these circumstances, RGCs show only transient sprouting, followed by continuous retrograde RGC degeneration. In the third group, after the optic nerve lesion, adult rats additionally received a sciatic nerve graft to the transected optic nerve stump. This allows some RGCs to regenerate an axon into the grafted nerve. In both groups, the time course of RGC survival and JUN, CREB, and FOS protein expression was monitored. In normal animals, JUN‐Immunoreactivity (JUN‐Ir) was not detectable in the retinal ganglion cell layer. JUN‐Ir was induced in about 70% of all FG‐positive RGCs 5 days after axotomy. The expression of JUN‐Ir started to decline 8 days after axotomy. Only a few JUN‐Ir‐positive RGCs were found after 2 weeks. In transplanted animals, however, the numbers of JUN‐Ir‐positive RGCs were significantly higher 2 and 3 weeks after transplantation compared to animals that exclusively received axotomy. Furthermore, in grafted rats about 70% of the regenerating RGCs expressed JUN‐Ir 2 weeks after grafting as compared to only 38% JUN‐positive RGCs among the surviving but not regenerating RGCs. In normal animals CREBP‐Ir was constitutively expressed in nearly all cells of the retinal ganglion cell layer. The decline in number of CREBP‐Ir‐positive cells paralleled the axotmy‐induced RGC death. FOS‐Ir‐positive cells were not found in the ganglion cell layer at any time. These results demonstrate a selective and transient JUN expression of RGCs after axotomy which is sustained during axonal regeneration. This suggests that sciatic nerve grafts are able to regulate the expression of JUN proteins in axotomized RGCs of adult rats. 1994 John Wiley & Sons, Inc.
Expression of NGF receptor and GAP‐43 mRNA in DRG neurons during collateral sprouting and regeneration of dorsal cutaneous nerves
Authors: Mearow K. M. , Kril Y. , Gloster A. , Diamond J.
Published: January 2005

The collateral sprouting of intact sensory axons and the regenertion of damaged ones differ in a number of respects. Regeneration is triggered by axotomy‐induced damage, probably involves the loss of a peripheral signal, and appears to occur independently of NGF, while collateral sprouting is evoked and sustained by an increase in a target‐driven signal, namely NGF. New findings strengthen the distinction between these two phenomena. Nerve growth factor receptor (NGFR) mRNA is increased in undamaged DRG neurons whose axons are sprouting into denervated skin. This response is related to an increased availablity of target‐derived NGF, a proposal supported by a number of findings including increased NGF mRNA in the denervated target. In contrast, we observed little or no change in the NGFR mRNA levels in regenerating neurons, consistent with the observations that NGF does not play a role in this process. However, increases in neuronal GAP‐43 mRNA are found during both regeneration and collateral sprouting, a result in keeping with the proposal that GAP‐43 is primarily associated with nerve growth, and the observation that GAP‐43 expression is not especially influenced by NGF. 1994 John Wiley & Sons, Inc.
Calcium regulation of gene expression in neuronal cells
Authors: Ghosh Anirvan , Ginty David D. , Bading Hilmar , Greenberg Michael E.
Published: January 2005

Long‐term adaptive changes in neurons following brief periods of neuronal activity are likely to involve changes in gene expression. The mechanisms of activity‐dependent gene expression have been explored in central neurons and the neuronal cell line PC12. Calcium influx through either NMDA receptors or voltage‐sensitive calcium channels leads to the rapid induction of a number of immediate‐early genes including c‐fos. Promoter analysis indicates that Ca2+ influx through different calcium channels activates distinct signaling pathways that either target the serum response element (SRE) or the calcium response element (CaRE) within the c‐fos promoter. Transcription through the CaRE requires the induced phosphorylation of the cAMP response element binding protein (CREB) at Ser133. This site on CREB is also phosphorylated in the suprachiasmatic nucleus in in vivo upon light stimulation. These observations suggest Ca2+ can regulate gene expression by multiple signaling pathways including one that involves the Ca2+‐dependent phosphorylation of the transcription factor CREB. 1994 John Wiley & Sons, Inc.
Excitatory interaction between glutamate receptors and protein kinases
Authors: Soderling T. R. , Tan S. E. , McGlade‐McCulloh E. , Yamamoto H. , Fukunaga K.
Published: January 2005

One of the most active areas of neurobiology research concerns mechanisms involved in paradigms of synaptic plasticity. A popular model for cellular leaning and memory is long term potentiation (LTP) in hippocamus. LTP requires postsynaptic influx of Ca2+ which triggers multiple biochemical pathways resulting in pre‐ and postsynaptic mechanisms enhancing long term synaptic efficiency. This article focuses on an acute postsynaptic Mechanism that can enhance responsiveness of glutamate receptors. Evidence is presented that calcium/calmodulin/dependent protein kinase II, the major potsynaptic density protein at excitatory glutaminergic synapses, can phosphorylate glutamate receptors and enhance ion current flowing through them. 1994 John Wiley & Sons, Inc.
Proteolytic activity, synapse elimination, and the Hebb synapse
Authors: Liu Y. , Fields R. D. , Fitzgerald S. , Festoff B. W. , Nelson P. G.
Published: January 2005

The Hebb synapse has been postulated to serve as a mechanism subserving both regulation of synaptic strength in the adult nervous system (long‐term potentiation and depression) and developmental activity‐dependent plasticity. According to this model, pre‐ and postsynaptic temporal concordance of activity results in strengthening of connections, while discordant activity results in synapse weakening. Evidence is presented that proteases and protease inhibitors may be involved in modification of synaptic strength. This leads to a modification of the Hebb assumptions, namely that postsynaptic activity results in protease elaboration with a consequent general reduction of synaptic connections to the active postsynaptic element. Further, presynaptic activity, if strong enough, induces local release of a protease inhibitor, such as protease nexin I, which neutralizes proteolytic activity and produces a relative preservation of the active input. This formulation produces many of the effects of the classical Hebbian construction, but the protease/inhibitor model suggests additional specific mechanistic features for activity‐dependent plasticity. 1994 John Wiley & Sons, Inc.