bluuebunny/crossref_metadata_2025 huggingface dataset:
Degeneration of photoreceptors in rhodopsin mutants of Drosophila
Authors: Leonard Debra S. , Bowman Valorie D. , Ready Donald F. , Pak William L.
Published: January 2005

Five different, well‐characterized mutants of the R1–6 rhodopsin gene (ninaE), which corresponds to the rod opsin gene of vertebrates, have been examined morphologically as a function of age (up to 9 weeks) to determine whether or not the photoreceptors degenerate and to assess the pattern of degeneration. Structural deterioration of R1–6 photoreceptors with age has been found in all five mutants. The structural pattern of degeneration is similar in the five mutants, but the time course of degeneration is allele dependent and varies greatly among the five, with the strongest alleles causing the fastest degeneration. The degeneration appears to be independent of either the illumination cycle to which the animals are exposed or the presence of screening pigments in the eye. Although the degeneration first appears in R1–6 photoreceptors, eventually R7/8 photoreceptors, which correspond to cones of vertebrates, are also affected. In many of these mutants, striking proliferations of membrane processes have been observed in the subrhabdomeric region of R1–6 photoreceptors. It is hypothesized that (1) this accumulation of membranes may be caused by the failure of newly synthesized membranes that are inserted into the base of microvilli to be assembled into R1–6 rhabdomeres and (2) this failure may be caused by the extremely low concentration of normal R1–6 rhodopsin in the nina E mutants. © 1992 John Wiley & Sons, Inc.
Sex‐dependent loss of projection neurons involved in avian song learning
Authors: Nordeen E. J. , Grace A. , Burek M. J. , Nordeen K. W.
Published: January 2005

In zebra finches, only males sing, and the neural regions controlling song exhibit prominent, hormone‐induced sex diffences in neuron number. In order to understand how sexual differentiation regulates neuron number within one song nucleus, the lateral magnocellular nucleus of the anterior neostriatum (IMAN), we studied the development of sex differences among IMAN neurons that project to the robust nucleus of the archistriatum (RA). The IMAN is implicated in song learning, and previous ontogenetic studies have indicated that males lose over 50% of their IMAN neurons during the juvenile song learning period. Based on developmental changes in both the extent of androgen accumulation within the IMAN and its appearance in Nissl‐stained tissue, it had been hypothesized that IMAN neuron loss was even greater in young females, resulting in sex differences in neuron number. However, this hypothesis has not been tested directly because the Nissl‐stained boundaries of the IMAN sometimes are ambiguous in young animals, and are not evident at all in adult females. To circumvent these problems, we employed the retrograde tracer fast blue to study the development of IMAN neurons defined on the basis of their projections to the RA. We find that the number of these IMAN‐RA projection neurons is much greater in adult males than in females, and that this sex difference develops during the juvenile period of sexual differentiation and song learning because a significant number of these neurons are lost in females but not in males. With respect to sexual differentiation, we conclude that masculinization (which is stimulated by the hormone estradiol) promotes the retention of IMAN‐RA projection neurons. In addition, our results indicate that any loss of IMAN neurons that may occur in young males does not include cells projecting to the RA. © 1992 John Wiley & Sons, Inc.
Transient expression of somatostatin peptide is a widespread feature of developing sensory and sympathetic neurons in the embryonic rat
Authors: Katz David M. , He Huajun , White Melissa
Published: January 2005

Previous studies from this and other laboratories demonstrated that many embryonic sensory ganglion cells in the rat transiently express the catecholamine synthesizing enzyme tyrosine hydroxylase (TH), a trait not expressed by most mature sensory neurons. We, therefore, sought to determine whether transient expression was uniquely associated with catecholaminergic traits, or, alternatively, whether embryonic ganglion cells transiently expressed peptidergic properties as well. Of the four peptides examined {somatostatin [somatotropin release inhibiting factor] (SRIF), galanin (Gal), calcitonin gene‐related peptide (CGRP), and substance P (SP)}, only SRIF was found to be transiently expressed during early stages of sensory gangliogenesis. Surprisingly, SRIF immunoreactivity was observed in virtually all cranial and spinal sensory ganglion cells on embryonic day (E) 12.5. In addition to perikaryal labeling, intense SRIF immunoreactivity was also observed in the central and peripheral processes of E12.5 sensory neurons, suggesting the peptide may be released from nerve endings. The time course of SRIF appearance in cranial ganglion cells paralleled that previously described for TH, and double labeling studies revealed extensive co‐localization of these two phenotypes. By E16.5, however, the number of neurons expressing SRIF had diminished markedly, indicating that SRIF is only transiently expressed by most sensory neurons during early stages of ganglion development. An unexpected finding was that transient expression of SRIF is also a prominent feature of sympathetic ganglion cells; however, the temporal pattern of staining in the sympathetic and sensory ganglia differed substantially. Whereas virtually no SRIF staining was observed in E12.5 sympathetics, the vast majority of cells in the E16.5 superior cervical ganglion (SCG) were labeled. This contrasted sharply with the adult SCG, in which only low levels of SRIF expression were found. These findings demonstrate that SRIF peptide is transiently expressed at high levels in peripheral sensory and sympathetic neurons during embryogenesis. The time course and widespread distribution of SRIF expression indicates that the peptide may play a role in early stages of ganglion cell growth and development. Moreover, these data, in conjunction with previous studies demonstrating SRIF immunoreactivity in developing central neurons, suggest that transient expression of this peptide is a common property of diverse neuronal cell types. © 1992 John Wiley & Sons, Inc.
Perturbed glial scaffold formation precedes axon tract malformation in Drosophila mutants
Authors: Jacobs J. Roger
Published: January 2005

The longitudinal glia (LG), progeny of a single glioblast, form a scaffold that presages the formation of longitudinal tracts in the ventral nerve cord (VNC) of the Drosophila embryo. The LG are used as a substrate during the extension of the first axons of the longitudinal tract. I have examined the differentiation of the LG in six mutations in which the longitudinal tracts were absent, displaced, or interrupted to determine whether the axon tract malformations may be attributable to disruptions in the LG scaffold. Embryos mutant for the gene prospero had no longitudinal tracts, and glial differentiation remained arrested at a preaxonogenic state. Two mutants of the Polycomb group also lacked longitudinal tracts; here the glia failed to form an oriented scaffold, but cytological differentiation of the LG was unperturbed. The longitudinal tracts in embryos mutant for slit fused at the VNC midline and scaffold formation was normal, except that it was medially displaced. Longitudinaltracts had intersegmental interruptions in embryos mutant for hindsight and midline. In hindsight, there were intersegmental gaps in the glial scaffold. In midline, the glial scaffold retracted after initial extension. LG morphogenesis during axonogenesis was abnormal in midline. Commitment to glial identity and glial differentiation also occurred before scaffold formation. In all mutants examined, the early distribution of the glycoprotein neuroglian was perturbed. This was indicative of early alterations in VNC pattern present before LG scaffold formation began. Therefore, some changes in scaffold formation may have reflected changes in the placement and differentiation of other cells of the VNC. In all mutants, alterations in scaffold formation preceded longitudinal axon tract formation. © 1993 John Wiley & Sons, Inc.
Enchancer detector analysis of the extent of genomic involvement in nervous system development in Drosophila melanogaster
Authors: Datta Sumana , Stark Karen , Kankel Douglas R.
Published: January 2005

We conducted a survey of the patterns of gene expression in the central nervous system (CNS) of larvae of the fruitfly Drosophila melanogaster to identify genes that may be important in the development of the CNS, aid in the recognition of basic organizing features that might underlie CNS development, and estimate the extent of the use of information encoded in the genome in the construction of the nervous system. A so‐called enhancer detector strategy was used to generate many thousands of lines containing a β‐galactosidase reporter gene. These lines were screened as third‐instar larvae for patterns of expression in the developing optic lobes and other portions of the CNS. Most of the lines recovered which evidence staining within the CNS could be included in one of a relatively small number of patterns. A random sample of 594 lines from the larger population screened was selected to quantify the relative frequencies of these patterns, and a more careful analysis of the changes in the patterns of expression with developmental time was done for representative lines of nine of the patterns. These studies demonstrated great variability in the patterns of gene expression as a function of developmental stage. Few, if any, lines showed β‐galactosidase activity limited to the optic lobes; similarly, few lines were identified in which staining was limited to only a small number of cells. Together with the limited number of patterns of gene expression seen, this suggests that in the larval CNS developmental pathways may be controlled by a combinatorial process of gene activity that involves the majority of the genome rather than by having a specific gene specify the fate of only a few neuronal precursors. © 1993 John Wiley & Sons, Inc.
Regeneration from crayfish phasic and tonic motor axonsin vitro
Authors: Egid Kathleen , Lnenicka Gregory A.
Published: January 2005

An explant culture system is described that allows examination of axonal growth from the tonically and phasically active motoneurons of the abdominal nerve cord of the crayfish. In this preparation, growth occurs from the cut end of the axon while the remainder of the motoneuron is undisturbed.In vitrogrowth from the branches of the third roots, which contain the axons from the tonic and phasic motoneurons of abdominal ganglia one through four, was verified as axonal by retrograde labeling of axons and neuronal somata within the nerve cord. Growth from the axons of phasic and tonic cells was observed as early as 24 h after plating and continued for an additional 7–10 days. The morphology and growth rates of the motor terminals differed between the tonic and phasic axons. The phasic axons grew significantly faster and branched more often than did the tonic motor axons. These differences in growth may be related to differences in motoneuron size or, may result from differences in electrical activity. Tonic motoneurons show spontaneous impulse activity for up to 6 days in culture, whereas phasic motoneurons show no spontaneous impulse activity. In addition, the differences in growth may be related to the morphological differences in tonic and phasic motor terminals observedin situ. © 1993 John Wiley & Sons, Inc.
Modulation of the enkephalinergic phenotype of rat sympathetic neurons by hormonal and transynaptic mechanisms
Authors: Henion Paul D. , Landis Story C.
Published: January 2005

Most sympathetic neurons contain one or more neuropeptides in addition to catecholamines. Although the regulation of catecholamines has been studied extensively, comparatively little is known about the regulation of neuropeptides. Since glucocorticoids and preganglionic innervation regulate catecholaminergic properties in chromaffin cells, we examined the effects of these factors on a co‐localized neuropeptide, leucine enkephalin (L‐Enk), in adult rat sympathetic neurons in vivo. Lowered serum glucocorticoid levels as a consequence of bilateral adrenalectomy resulted in a reduction of ganglionic L‐Enk content that was reversed by exposure of adrenalectomized animals to the synthetic glucocorticoid, dexamethasone. Surgical denervation of the SCG eliminated L‐Enk‐IR preganglionic fibers and caused a dramatic increase in the number of L‐Enk‐IR neurons. Inhibition of the enkephalinergic component of the preganglionic innervation by chronic exposure to the opiate receptor antagonist naloxone increases the number of L‐Enk‐IR cell bodies and total ganglionic L‐Enk content. None of the experimental manipulations noticeably altered the number or distribution of NPY‐IR neurons, suggesting that the effects of glucocorticoids and the innervation on ganglionic L‐Enk levels were specific and not simply an alteration of the biosynthetic state of the cells. These results demonstrate that circulating glucocorticoids and the preganglionic innervation regulate L‐Enk levels in sympathetic neurons. Since both glucocorticoid levels and preganglionic activity are known to be altered by stressful stimuli, acute regulation of sympathetic L‐Enk levels may constitute an important component of the autonomic response to stress. © 1993 John Wiley & Sons, Inc.
Rin, a novel cell‐surface protein that labels reticular neurons early in chick neurogenesis
Authors: Chang Susannah , Raible David W.
Published: January 2005

Rin is a large cell‐surface glycoprotein that we have recently purified from chick brain, with a molecular weight of approximately 200 kD. Protein microsequence obtained from immunopurified rin does not match any sequences in the Genbank data base. Based on the sequences information and on its localization in the early chick embryo, rin is a novel cell‐surface protein. Rin is expressed on the surface of many, but not all, axons in the developing chick nervous system. In the chick hind‐brain, rin is expressed on reticular neurons, the first neurons to extend axons within the brain. Cranial motorneurons, which extend axons just a few stages later, do not express rin. Rin‐positive axons pioneer the caudal section of the medial longitudinal fasciculus. The very first rin‐positive axons that reach the floorplate do not enter the floorplate, but remain ipsilateral. Some of the next immunopositive axons to reach the floorplate do cross the midline, often with an alteration in trajectory, and often extending within the floorplate for some distance before reaching the other side. The failure of the very first rin‐positive axons to cross the floorplate, and the changes in trajectory observed when the next axons extend onto the floorplate, suggests that early differentiating neurons cross the midline with some difficulty. 1994 John Wiley & Sons, Inc.
The survival of rat cerebral cortical neurons in the presence of trophic APP peptides
Authors: Yamamoto Kyoko , Miyoshi Toshio , Yae Tetsuji , Kawashima Kazuaki , Araki Hiroaki , Hanada Kazunori , Otero Deborah A. C. , Roch Jean‐Marc , Saitoh Tsunao
Published: January 2005

One function of Alzheimer amyloid protein precursor (APP) is the regulation of growth and differentiation in several types of cells, including fibroblasts, PC12 cells, and neurons. This activity is represented by a small stretch of amino acids in the center of the molecule around RERMS. The APP 17‐mer peptide containing the RERMS domain supported survival and neurite extension of rat cortical neurons in a dose‐dependent and sequence‐specific manner. The APP fragment synthesized inEscherichia colisupported the survival and neurite extension of rat cortical neurons, whereas the mutant APP fragment lacking the 30 amino acids around the RERMS domain had drastically reduced activity to support the survival and neurite extension. The current study established APP as a neuron survival factor and determined that the sequence around RERMS is important for this function. © 1994 John Wiley & Sons, Inc.
FGF and EGF are mitogens for immortalized neural progenitors
Authors: Kitchens Daniel L. , Snyder Evan Y. , Gottlieb David I.
Published: January 2005

Individual neural progenitors, derived from the external germinal layer of neonatal murine cerebellum, were previously immortalized by the retrovirus‐mediated transduction of avian myc (v‐myc). C17‐2 is one of those cloanl multipotent progenitor cell lines (Snyder et al., 1992, Cell 68: 33–51; Ryder et al., 1990, J. Neurobiol. 21:356–375). When transplanted into newborn mouse cerebellum (CB), the cells participate in normal CB development; they engraft in a cytoarchitecturally appropriate, nontumorigenic manner and differentiate into multiple CB cell types (neuronal and glial) similar to endogenous progenitors (Snyder et al., 1992, as above). They also appear to engraft and participate in the development of multiple other structures along the neural axis and at multiple other stages (Snyder et al., 1993, Soc. Neurosci. Abstr. 19). Thus conclusions regarding these immortalized progenitors may be applicable to endogenous neural progenitors in vivo. To help identify and analyze factors that promote differentiation of endogenous progenitors, we first investigated the ability to maintain C17‐2 cells in a defined, serum‐free medium (N2). The cell survive in vitro in N2 but undergo mitosis at a very low rate. Addition of epidermal growth factor (EGF), however, either from mouse submaxillary gland or the human recombinant protein, appreciably stimulates thymidine incorporation and cell division approximately threefold. Basic fibroblast growth factor (bFGF) is an even more potent mitogen, promoting thymidine incorporation, cell division, and a net increase in cell number equal to that in serum. Both EGF and bFGF are active at very low nanomolar concentrations, suggesting that they interact with their respective receptors rather than a homologous receptor system. The findings demonstrate that C17‐2 cells can be maintained and propagated in a fully defined medium, providing the basis for analysis of other growth and differentiation factors. That EGF and particularly bFGF are mitogenic for these cells is in accord with recent observations on primary neural tissue (Reynolds and Weiss, 1992, Science 255:1707–1710; Kilpatrick and Barlett, 1993, Neuron 10:255–265; Ray et al., 1993, Proc. Natl. Acad. Sci. U.S.A. 90: 3602–3606) suggesting that bFGF and EGF responsiveness may be fundamental properties of neural progenitors. 1994 John Wiley & Sons, Inc.
Selective expression of glionexin, a glial glycoprotein, in insect mechanoreceptors
Authors: Field L. H. , Meyer M. R. , Edwards J. S.
Published: January 2005

The distribution of a glial cell‐associated glycoprotein, glionexin (GX), on sensory receptors of the adult cricket Acheta domesticus is described, using the monoclonal antibody 5B12 as an immunohistochemical probe. GX was previously shown to be widely distributed in the embryo and to persist in the postembryonic to adult central nervous system. Here we demonstrate that it is restricted in the adult periphery to three subclasses of mechano‐receptor sensilla: large socketed hair mechanoreceptors, their associated campaniform sensilla, and chordotonal organs. GX was not detected in photoreceptors, chemoreceptors, or other mechanoreceptors. The pattern of distribution differs significantly within the three subclasses of mechanoreceptors. In the hair and campaniform receptors GX is restricted to the extracellular space among glial cells clustered around the axon hillock region, but in chordotonal organs it surrounds the scolopidium at the tip of dendrites. The highly restricted distribution of GX in the periphery suggests possible functions that include mechanical stability of the sensory apparatus and ionic homeostasis in the respective neuronal spike‐generating regions. The developmental modulation of GX expression is taken to imply multiple functions for the molecule during the life of the insect. 1994 John Wiley & Sons, Inc.
Sexual differentiation in the CNS of the moth, Manduca sexta. II. Target dependence for the survival of the imaginal midline neurons
Authors: Thorn Robert S. , Truman James W.
Published: January 2005

While majority of the neurons in the adult nervous system of the moth Manduca sexta are produced postembryonically, little is known about how these cells interact with their targets during development. Few of these cells are motor neurons; most of Manduca's adult motor neurons are respecified larval motor neurons do develop postembryonically, including a large class of mixed neurosecretory and motor neurons called the imaginal midline neurons (IMNs). A subset of these cells show an unusual pattern of sex‐specific development and survival (Thorn and Truman, 1994, J. Neurobiol. in press), which led us to suspect that factors extrinsic to the cells were controlling their fates. We analyzed one such potential factor by altering the contacts between a subset of these developing IMNs and their adult‐specific target, the male sperm duct.

When we transected the nerve that innervated the sperm duct in the pupa, we observed a loss of many sperm duct IMNs. In contrast, a transection of the same nerve in larvae showed no neuron loss. Immunocytochemistry showed that the pupal nerve transections were accompanied by a loss of axon endings on the sperm duct, while the larval nerve transections showed no such loss. Using local hormone application to slow the development of the sperm duct while leaving the nerve intact still resulted in a loss of IMNs. These results suggest that these IMNs need contact with a robust developing target in the pupa to survive metamorphosis. 1994 John Wiley & Sons, Inc.
Re‐evaluation of the absolute threshold and response mode of the most sensitive know “vibration” detector, the cockroach's subgenual organ: A cochlea‐like displacement threshold and a direct response to sound
Authors: Shaw Stephen R.
Published: January 2005

Earlier accounts claim from indirect measurements that the subgenual organ (SGO) in the proximal tibia of the cockroach leg can detect vibrational displacements down to 0.002 mm, two orders of magnitude below the threshold for vertebrate hair cells in the cochlea. The SGO vibration threshold is redetermined here more directly by a new method on a cantilever beam, while controlling for particular acoustic and vibrational artifacts that might have compromised earlier efforts. The threshold is revised upwards to about 0.2 mm in the most sensitive preparation, about the same as cochlea. Recently, it has been determined that the cockroach SGO also has an auditory response, and the data here on subthreshold summation and response‐intensity relationships provide further evidence that sound and contact vibration are both sensed by the same receptor neurons. Direct measurements rule out the prevailing hypothesis that sound is detected indirectly as induced vibration of the ground, and also weigh strongly against any significant involvement of generalized leg resonance in acoustic pick‐up. The results fit with a recent proposal that the auditory response is direct, and that acoustic fluctuations inside the tracheae may be the primary response mode in the transduction of both vibration and sound. 1994 John Wiley & Sons, Inc.
Involvement of protein kinase C in the axonal growth‐promoting effect on spinal cord neurons by target‐derived astrocytes
Authors: Qian Jiang , Wang Hoau‐Yan , Fischer Itzhak , Friedman Eitan , Levitt Pat
Published: January 2005

Astroglial cells participate in a variety of developmental events during neuronal morphogenesis. We have shown that axonal, but not dendritic, outgrowth of spinal cord neurons can be promoted by a diffusible factor or factors secreted from target region‐derived cerebellar astroglia in vitro in comparison with spinal astroglia. In the present study, we examined the involvement of protein kinase C (PKC) in the axon‐promoting effect by astroglia. The inhibition of PKC by sphingosine or by the phorbol ester 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) at high concentration greatly reduced the mean axonal length of spinal neurons cultured in medium conditioned by cerebellar astroglia (SCn‐CBg), while activation of PKC by TPA at low concentration, or by retinoic acid, was not additive to the glial effect. The activation of PKC by TPA or retinoic acid promoted axon growth of spinal neurons cultured in medium conditioned by spinal astroglia (SCn‐SCg), which otherwise would not be as supportive for axon growth as cerebellar astroglia. Western blotting and PKC activity assays showed that there was a trend for increased PKC activity and protein levels (in particular, PKCβ) in SCn‐CBg cultures, which correlated with enhanced axon growth. Inhibition of PKC by sphingosine appeared to decrease protein levels, especially PKCβ, which correlated with suppressed axon outgrowth. In SCn‐SCg cultures, phorbol ester activation of PKC increased both activity and protein levels of both PKCα and PKCβ. This activation correlated with stimulated axonal outgrowth. These results suggest that the glial signaling that regulates specific axonal outgrowth by target astroglia is mediated in part by the PKC second messenger system. © 1994 John Wiley & Sons, Inc. 1994 John Wiley & Sons, Inc.
A human glial hybrid cell line differentially expressing genes subserving oligodendrocyte and astrocyte phenotype
Authors: McLaurin Joanne , Trudel Geralyn C. , Shaw Ivan T. , Antel Jack P. , Cashman Neil R.
Published: January 2005

We have developed a series of immortal human‐human hybrid cell lines that express phenotypic characteristics of primary oligodendrocytes, by fusing a 6‐thioguanine–resistant mutant of the human rhabdomyosarcoma RD with adult human oligodendrocytes by a lectin‐enhanced polyethylene glycol procedure. Hybrids were selected in an aminopterin‐containing media. In contrast to the tumor parent cells, a hybrid clone M03.13 expressed surface immunoreactivity for galactosyl cerebroside and intracellular immunoreactivity for myelin basic protein (MBP), proteolipid protein (PLP), and glial fibrillary acidic protein (GFAP). Serum deprivation or chronic treatment with a protein kinase C activator 4‐β‐phorbol 12‐myristate 13‐acetate (PMA), but not dibutyl cyclic adenosine monophosphate induced coordinate up‐regulation or de novo induction of oligodendrocyte phenotypic markers with concomitant down‐regulation of GFAP expression. Consistent with immunohistochemical studies, northern blot analysis demonstrated that both MBP and PLP mRNA were up‐regulated in MO3.13 cells by PMA treatment. M03.13 cells provide an immortalized clonal model system suitable for study of gene expression subserving oligodendrocyte and astrocyte phenotypes. © 1995 John Wiley & Sons, Inc.
Spontaneous calcium transients regulate neuronal plasticity in developing neurons
Authors: Spitzer Nicholas C. , Olson Eric , Gu Xiaonan
Published: January 2005

Calcium ions play critical roles in neuronal differentiation. We have recorded transient, repeated elevations of calcium in embryonic Xenopus spinal neurons over periods of 1 h in vitro and in vivo, confocally imaging fluo 3‐loaded cells at 5 s intervals. Calcium spikes and calcium waves are found both in neurons in culture and in the intact spinal cord. Spikes rise rapidly to approximately 400% of baseline fluorescence and have a double exponential decay, whereas waves rise slowly to approximately 200% of baseline fluorescence and decay slowly as well. Imaging of fura 2‐loaded neurons indicates that intracellular calcium increases from 50 to 500 nM during spikes. Both spikes and waves are abolished by removal of extracellular calcium. Developmentally, the incidence and frequency of spikes decrease, whereas the incidence and frequency of waves are constant. Spikes are generated by spontaneous calcium‐dependent action potentials and also utilize intracellular calcium stores. Waves are produced by a mechanism that does not involve classic voltage‐dependent calcium channels. Spikes are required for expression of the transmitter GABA and for potassium channel modulation. Waves in growth cones are likely to regulate neurite extension. The results demonstrate the roles of a novel signaling system in regulating neuronal plasticity, that operates on a time scale 104 times slower than that of action potentials. © 1995 John Wiley & Sons, Inc.
Multiple forms of long‐term potentiation and multiple regulatory sites of N‐methyl‐D‐aspartate receptors: Role of the redox site
Authors: Gozlan H. , Khazipov R. , Ben‐Ari Y.
Published: January 2005

Long‐term potentiation (LTP) is a form of synaptic plasticity thought to be involved in learning and memory. Althrough extensively studied, mainly in the CA1 region of the hippocampus, the mechanisms underlying the induction and expression of LTP are poorly elucidated. This is probably due to the fact that LTP is not a unique process and indeed recent studies have shown that several forms of LTP could be generated depending on the experimental conditions. Furthermore, LTP is generally associated with a long‐lasting increase of the synaptic efficacy of AMPA receptors but an increasing number of data also suggested that NMDA receptors could be potentiated as well. NMDA receptor responses are modulated by a large number of extracellular and intracellular events, providing additional possibilities for the generation of LTP. The role of these different modulatory sites of the NMDA receptor and their relation with LTP are reviewed with a particular attention to the redox site which seems to be a selective target to distinguish between AMPA and NMDA‐LTP. © 1995 John Wiley & Sons, Inc.
The neural cell adhesion molecule and synaptic plasticity
Authors: Doherty Patrick , Fazeli Mohammed S. , Walsh Frank S.
Published: January 2005

Highly stereotyped patterns of neuronal connections are laid down during the development of the nervous system via a range of activity independent and activity dependent mechanisms. Whereas the coarse hard‐wiring of the nervous system appears to rely on molecular recognition events between the neuron, its pathway, and its target, the establishment of precisely patterned functional circuits is thought to be driven by neuronal activity. In this review we discuss the role that the neuronal cell adhesion molecule (NCAM) plays in morphological plasticity. Recent studies on NCAM and its probable species homologue in Aplysia (apCAM) suggests that an individual CAM can function to both promote synaptic plasticity and maintain the structure of the synapse. In the adult brain, changes between stability and plasticity are likely to underlie dynamic morphological changes in synaptic structures associated with learning and memory. In this review we use NCAM as an example to illustrate mechanisms that can change the function of an individual CAM from a molecule that promotes plasticity to one that does not. We also discuss evidence that NCAM promotes plasticity by activating a conventional signal transduction cascade, rather than by modulating adhesion perse. Finally, we consider the evidence that supports a role for NCAM in learning and memory. © 1995 John Wiley & Sons, Inc.
Developmental expression of heterotrimeric G proteins in the nervous system of Manduca sexta
Authors: Copenhaver P. F. , Horgan A. M. , Nichols D. C. , Rasmussen M. A.
Published: January 2005

The heterotrimeric G proteins are a conserved family of guanyl nucleotide‐binding proteins that appear in all eukaryotic cells but whose developmental functions are largely unknown. We have examined the developmental expression of representative G proteins in the developing nervous system of the moth Manduca sexta. Using affinity‐purified antisera against different Gα subunits, we found that each of the G proteins exhibited distinctive patterns of expression within the developing central nervous system (CNS), and that these patterns underwent progressive phases of spatial and temporal regulation that corresponded to specific aspects of neuronal differentiation. Several of the G proteins examined (including Gsα and Goα) were expressed in an apparently ubiquitous manner in all neurons, but other proteins (including Giα) were ultimately confined to a more restricted subset of cells in the mature CNS. Although most of the G proteins examined could be detected within the central ganglia, only Goα‐related proteins were seen in the developing peripheral nerves; manipulations of G protein activity in cultured embryos suggested that this class of G protein may contribute to the regulation of neuronal motility during axonal outgrowth. Goα‐related protein were also localized to the developing axons and terminals of the developing adult limb during metamorphosis. These intracellular signaling molecules may, therefore, play similar developmental roles in both the embryonic and postembryonic nervous system. © 1995 John Wiley & Sons, Inc.
In situ hybridization reveals transient laminin B‐chain expression by individual glial and muscle cells in embryonic leech central nervous system
Authors: Luebke Anne E. , Dickerson Ian M. , Muller Kenneth J.
Published: January 2005

Laminin, which strongly stimulates axon outgrowth in vitro, appears transiently within the central nervous system (CNS) in embryos. After CNS injury, laminin reportedly reappears along axonal pathways only in animal species in which central axon regeneration is successful, including the leech Hirudo medicinalis. Although glia have been suspected of making CNS laminin, in adult leeches glia are not required for laminin synthesis and evidently microglia, not present in the early embryo, produce laminin. To determine which embryonic cells make laminin, a 1.2 kb DNA fragment of leech laminin B1 chain, with homology to Drosophila, human, and mouse B1 laminins and rat S laminin, was isolated using reverse‐transcription and degenerate polymerase chain reaction (PCR) cloning. In situ hybridization revealed that laminin expression began before embryonic day 8, and by days 8 and 9 it was seen in paired CNS muscle cells. By late day 9, the two neuropil glial cells began to express laminin. Lucifer Yellow dye was injected intracellularly and muscle cells stimulated to contract, confirming the identities of muscle and glial cells. Packet glial cells began to express B1 laminin by embryonic day 12. By day 15, the cells of the perineurial sheath expressed B1 laminin, whereas it was no longer detectable in CNS muscle and glia. The results agree with published immunohistochemistry showing laminin within the CNS among growing axons by day 8, and only later in the perineurial sheath, by which time laminin disappears from within the CNS. Therefore, different cells synthesize laminin in the embryo and during repair in adults. © 1995 John Wiley & Sons, Inc.
Octopamine mediates rapid stimulation of protein kinase A in the antennal lobe of honeybees
Authors: Hildebrandt Herbert , Müller Uli
Published: January 2005

In the honeybee octopamine mediates mechanisms of arousal that interfere with the appetitive proboscis extension response to food‐indicating chemosensory stimuli. This study demonstrates that injections of octopamine or cyclic adenosine monophosphate (cAMP) into the primary chemosensory neuropil of the honeybee, the antennal lobe, evokes a rapid and transient activation of cAMP‐dependent protein kinase (PKA). Other monoamines detectable in the antennal lobe, dopamine and serotonin, do not affect the level of PKA activity. Stimulation of the bees' antenna with the appetitive stimulus water or sucrose solution in vivo also causes a short‐term activation of PKA in the antennal lobe. The increased PKA activity can be detected immediately (0.5 s) after stimulation but reverts to the basal level within 3 s. This effect can be abolished by monoamine depletion with reserpine. Since octopamine is the only monoamine that stimulates PKA, it appears to mediate the PKA activation after sucrose stimulus and may contribute to the processing of this chemosensory input. © 1995 John Wiley & Sons, Inc.
Regressive development in neuronal structure during song learning in birds
Authors: Nixdorf‐Bergweiler B. E. , Wallhäusser‐Franke E. , Devoogd T. J.
Published: January 2005

We investigated the development of spiny neurons in the lateral magnocellular nucleus of the anterior neostriatum before, during, and after song learning in male zebra finches (Taeniopygia guttata). The frequency of dendritic spines, dendritic field size, and branching characteristics were quantified at different ages in Golgi‐stained tissue using a three‐dimensional computerized tracing system. During development, overall spine frequencies increase between 3 and 5 weeks and decrease thereafter. In particular, spine frequencies of middle segments decrease significantly by 14% between 5 and 7 weeks posthatching (p = 0.017). A further reduction of 48% occurs between 7 weeks and adulthood (p < 0.001), resulting in a spine reduction of 56% on middle segments between 35 days of age and adulthood. In addition to the reduction of spine frequencies, we find regressive events also on some of the neuronal parameters that we have quantified. In general, dendrites of adult animals terminate closer to the cell body than those of 7‐, 5‐, or 3‐week‐old birds. Whereas no changes in segment length of first‐ and second‐order dendrites have been identified, third‐order dendrites end 19% closer to the cell body in adults than in younger birds (p < 0.024). Second‐order dendrites in adult animals branch less frequently than in 3‐week‐old animals (35%, p = 0.017). There is also a trend of a smaller number of tertiary branches in adulthood compared with 3‐week‐old birds (41%, p = 0.060). The morphological changes may be related to the function of this nucleus and the sensitive phase for song acquisition. © 1995 John Wiley & Sons, Inc.
Synapse formation and function: Insights from identified leech neurons in culture
Authors: Fernández‐de‐Miguel Francisco , Drapeau Pierre
Published: January 2005

Identified leech neurons in culture are providing novel insights to the signals underlying synapse formation and function. Identified neurons from the central nervous system of the leech can be removed individually and plated in culture, where they retain their characteristic physiological properties, grow neurites, and form specific synapses that are directly accessible by a variety of approaches. Synapses between cultured neurons can be chemical or electrical (either rectifying or not) or may not form, depending on the neuronal identities. Furthermore, the characteristics of these synapses depend on the regions of the cells that come into contact. The formation and physiology of synapses between the Retzius cell and its partners have been well characterized. Retzius cells form purely chemical, inhibitory synapses with pressuresensitive (P) cells where serotonin (5‐HT) is the transmitter. Retzius cells synthesize 5‐HT, which is stored in vesicles that recycle after 5‐HT is secreted on stimulation. The release of 5‐HT is quantal, calcium‐dependent, and shows activity‐dependent facilitation and depression. Anterograde and retrograde signals during synapse formation modify calcium currents, responses to 5‐HT, and neurite outgrowth. The nature of these synaptogenic signals is being elucidated. For example, contact specifically with Retzius cells induces a localized selection of transmitter responses in postsynaptic P cells. This effect is signaled by tyrosine phosphorylation prior to synapse formation. © 1995 John Wiley & Sons, Inc.
What we have learned from the study of learning in the leech
Authors: Sahley Christie L.
Published: January 2005

The use of invertebrate preparations has contributed greatly to our understanding of the neural basis of learning. The leech is especially useful for studying behavioral changes and their underlying neuronal mechanisms. Learning in the leech is essentially identical to that found in other animals, both vertebrate and invertebrate. Using anatomical and physiological techniques on leeches as they learn, we have begun to characterize the properties of individual neurons and neuronal networks that play a role in learning. We have been able to show two neuronal mechanisms that have not been previously associated with associative conditioning. The first has to do with the importance of contingency: one stimulus [the conditional stimulus (CS)] becomes associated with a second stimulus [the unconditional stimulus, (US)] in proportion to the ability of the CS to predict the US. We have found that important properties for encoding predictability, such as circuit reconfiguration, may lie in the US pathway. The firing of the serotonergic Retzius cells is taken as the US; consistent CS prediction of a US prevents “dropout” of a critical component of one US pathway. Throughout training, predicted USs continue to elicit a barrage of action potentials in these cells. Recurring unpredicted USs degrade both the learning and the response of the Retzius cell to the US. A second insight is that at least two US pathways contribute to learning, the Retzius cell pathway and the nociceptive (N) cell pathway. This second pathway persists after the elimination of the Retzius cell pathway. The observation of multiple US pathways raises a host of issues concerning CS–US convergence and the functional significance of distinct US pathways, and our results are discussed in terms of implications to current models of learning. © 1995 John Wiley & Sons, Inc.
Localization of tissue plasminogen activator mRNA in the developing rat cerebellum and effects of inhibiting tissue plasminogen activator on granule cell migration
Authors: Ware J. H. , DiBenedetto A. J. , Pitman R. N.
Published: January 2005

Tissue plasminogen activator (tPA) mRNA was localized in the developing cerebellum and the potentials role of tPA in migration of cerebellar granule cells was investigated. Proteolytic assays and Northern blots showed little variation in levels of tPA proteolytic activity or tPA mRNA expression in the developing cerebellum. The distribution of cerebellar tPA mRNA at different ages was visualized by in situ hybridization histochemistry. At postnatal day 7 (P7), most labeled cells were in the internal granule layer or developing white matter, and very few if any premigratory granule cells contained tPA mRNA. Although the molecular layer contained labeled cells at all ages, cell counts indicated that a greater percentage of cells in the molecular layer contained tPA mRNA during adulthood than during the period of granule cell migration. The most striking change in tPA mRNA expression was in Purkinje neurons, most of which began to express tPA mRNA between P7 and P14. The potential role of tPA in granule cell migration was investigated by performing migration assays in cerebellar slice explants in the presence or absence of protease inhibitors. The presence of inhibitors did not affect the distance that granule cells migrated. Data in the present study do not support a role for tPA in granule neuron migration; however, they do indicate that tPA is both spatially and temporally regulated during cerebellar development. Possible functions of tPA in the cerebellum are discussed. © 1995 John Wiley & Sons, Inc.
A mouse homolog of dunce, a gene important for learning and memory in drosophila, is preferentially expressed in olfactory receptor neurons
Authors: Cherry James A. , Davis Ronald L.
Published: January 2005

The dunce (dnc) gene in Drosophila codes for a cyclic adenosine monophosphate‐specific phosphodiesterase (PDE). Flies with a mutation at this locus exhibit severe deficits in learning and memory. We have begun to analyze the neural distribution of mammalian homologs of dnc in the mouse. Surprisingly, in situ hybridization and northern blotting using a probe specific for one of the four mammalian dnc homologs (mPDE2) reveals high levels of expression in the olfactory neuroepithelium. Anti mPDE2 antibody confirms that this PDE protein is abundant in the axons and dendrites of the olfactory receptor neurons but is conspicuosly absent from the cilia, where the initial events in olfactory signal transduction occur. Lower levels of mPDE2 were also detected throughout the brain and in the testis. These findings suggest an important modulatory role for mPDE2 in mammalian olfaction. © 1995 John Wiley & Sons, Inc.
Human schwann cells in vitro. I. Failure to differentiate and support neuronal health under co‐culture conditions that promote full function of rodent cells
Authors: Morrissey T. K. , Bunge R. P. , Kleitman N.
Published: January 2005

Schwann cells (SCs) play critical roles in regeneration after injury to the peripheral nervous system and can also induce axonal regeneration in the central nervous system. Transplantation of purified SCs into sites of neural injury in rodents has confirmed the remarkable ability of these cells to promote axonal regrowth, suggesting that human application of SC transplantation could be valuable. In this report, we have compared the functional capacities of SCs derived from adult human and rodent nerves by maintaining SCs from these two sources in culture with sensory neurons. We noted that techniques commonly in use for maintaining pure rat SC populations are not sufficient to sustain populations of human SCs free of fibroblasts. In these co‐cultures, human SCs express a limited profile of characteristic behaviors and they proliferate more slowly than rat SCs in response to axonal contact, Slow SC proliferation, relative to that of contaminating fibroblasts, leads to a high proportion of fibroblasts in the cultures. After 3 to 4 weeks of co‐culture with neurons, human SCs express extracellular matrix molecules, but only partially ensheathe axons, whereas rat SCs differentiate, form basal lamina, and ensheathe or myelinate axons. Co‐culture of sensory neurons with human (but not rat) SC preparations (or conditioned medium therefrom) leads to a progressive neuronal atrophy characterized by shrinking neuronal cells bodies and a decrease in the density of the neurite network in the culture dish. As the divergent effects of human and rat SCs on neuronal health were also observed in co‐cultures with human sensory neurons, these effects reflect differences between the rat and human‐derived SC populations, rather than a species mismatch between SCs and neurons. The marked differences in behavior observed between rat and human SCs derived by the same methods requires further exploration if human‐derived SCs are to be considered in the treatment of disease. In a companion article we report experiments that define culture conditions more effective in promoting human SC function in vitro. © 1995 John Wiley & Sons, Inc.