Distinct migratory behavior of early‐ and late‐born neurons derived from the cortical ventricular zoneHatanaka, Yumiko; Hisanaga, Shin‐Ichi; Heizmann, Claus W.; Murakami, Fujio
doi: 10.1002/cne.20256pmid: 15389616
Time‐lapse studies indicate that ventricular zone (VZ)‐derived cells show two migratory modes in the cerebral cortex at different stages of mammalian embryogenesis: somal translocation and locomotion. We carried out a systematic analysis to examine whether the migratory behavior of cortical neurons derived from the cortical VZ is stage‐dependent. We labeled VZ cells of mouse embryos with green fluorescent protein (gfp) ‐encoding plasmids by in utero electroporation and evaluated the labeled cells after appropriate survival periods. After electroporation at either embryonic day (E) 12.5 or E15.5, GFP+ VZ cells were initially spindle‐shaped and radially oriented. After leaving the VZ, they transformed into round or horizontally oriented fusiform neurons with many short processes. They then seemed to gradually change into radially oriented bipolar cells as they moved upward. Whereas the earliest emigrants from the VZ labeled at E12.5 (early‐born neurons) reached the top of the cortical plate (CP) after these changes, VZ cells labeled at E15.5 (late‐born neurons) further migrated along the length of radial fibers to reach the top of the CP. A dominant negative form of the gene for cyclin‐dependent kinase 5 (Cdk5DN) was then introduced into VZ cells. Transfection of E12.5 VZ with cdk5dn did not disrupt the migration of the early‐born neurons. However, this caused a failure in migration of the late‐born neurons, although they transformed into bipolar shapes in the intermediate zone. Thus, there appear to be at least two distinct migratory phases of cortical neurons: one common to the early‐ and late‐born neurons, and the other specific to late‐born neurons and Cdk5‐dependent. J. Comp. Neurol. 479:1–14, 2004. © 2004 Wiley‐Liss, Inc.
Differential expression of p120 catenin in glial cells of the adult rat brainChauvet, Norbert; Privat, Alain; Prieto, Monica
doi: 10.1002/cne.20301pmid: 15389614
p120 catenin (p120ctn) is involved in the regulation of cadherin‐mediated adhesion and the dynamic organization of the actin cytoskeleton by modulating RhoGTPase activity. We have previously described the distribution of p120ctn during rat brain development and provided substantial evidence for the potential involvement of p120ctn in morphogenetic events and plasticity in the central nervous system. Here, we analyzed the cellular and ultrastructural distribution of p120ctn in glial cells of the adult rat forebrain. The highest intensity of immunostaining for p120ctn was found in cells of the choroid plexus and ependyma and was mainly restricted to the plasma membrane. However, p120ctn was almost absent from astrocytes. In contrast, in tanycytes, a particular glial cell exhibiting remarkable morphological plasticity, p120ctn, was localized at the plasma membrane and also in the cytoplasm. We show that a large subpopulation of oligodendrocytes expressed multiple isoforms, whereas other neural cells predominantly expressed isoform 1, and that p120ctn immunoreactivity was distributed through the cytoplasm and at certain portions of the plasma membrane. Finally, p120ctn was expressed by a small population of cortical NG2‐expressing cells, whereas it was expressed by a large population of these cells in the white matter. However, in both regions, proliferating NG2‐positive cells consistently expressed p120ctn. The expression of p120ctn by cells of the oligodendrocyte lineage suggests that p120ctn may participate in oligodendrogenesis and myelination. Moreover, the expression of p120ctn by various cell types and its differential subcellular distribution strongly suggest that p120ctn may serve multiple functions in the central nervous system. J. Comp. Neurol. 479:15–29, 2004. © 2004 Wiley‐Liss, Inc.
Neurogranin is expressed by principal cells but not interneurons in the rodent and monkey neocortex and hippocampusSingec, Ilyas; Knoth, Rolf; Ditter, Margarethe; Volk, Benedikt; Frotscher, Michael
doi: 10.1002/cne.20302pmid: 15389613
As a substrate of protein kinase C (PKC), neurogranin (NG) is involved in the regulation of calcium signaling and activity‐dependent plasticity. Recently, we have shown that, in the rodent cerebellum, NG is exclusively expressed by γ‐aminobutyric acidergic Golgi cells, whereas, in the monkey cerebellum, brush cells were the only neuronal population expressing NG (Singec et al. [2003] J. Comp. Neurol. 459:278–289). In the present study, we analyzed the neocortical and hippocampal expression patterns of NG in adult mouse (C57Bl/6), rat (Wistar), and monkey (Cercopithecus aetiops). By using immunocytochemistry and nonradioactive in situ hybridization, we demonstrate strong NG expression by principal cells in different neocortical layers and in the hippocampus by granule cells of the dentate gyrus and pyramidal neurons of CA1–CA3. In contrast, double‐labeling experiments in rodents revealed that neocortical and hippocampal interneurons expressing glutamate decarboxylase 67 (GAD67) were consistently devoid of NG. In addition, by using antibodies against parvalbumin, calbindin, and calretinin, we could demonstrate the absence of NG in interneurons of monkey frontal cortex and hippocampus. Together these findings corroborate the idea of different calcium signaling pathways in excitatory and inhibitory cells that may contribute to different modes of synaptic plasticity in these neurons. J. Comp. Neurol. 479:30–42, 2004. © 2004 Wiley‐Liss, Inc.
Up‐regulation of activated macrophages in response to degeneration in the taste system: Effects of dietary sodium restrictionMcCluskey, Lynnette Phillips
doi: 10.1002/cne.20307pmid: 15389612
Dietary sodium restriction combined with unilateral chorda tympani nerve section leads to a rapid and specific decrease in neurophysiological taste responses to sodium in the contralateral, intact chorda tympani (Hill and Phillips [1994] J. Neurosci. 14:2904–2910). Previous work demonstrated that dietary sodium restriction may induce these early functional deficits by inhibiting immune activity after denervation (Phillips and Hill [1996] Am. J. Physiol. 271:R857–R862). However, little is known about the leukocyte response to denervation of taste buds in fungiform papillae. In the current study, it was hypothesized that T cells and macrophages are increased in the tongue after unilateral denervation in control‐fed but not sodium‐restricted animals. Adult, specified pathogen‐free rats received unilateral chorda tympani nerve section or sham section followed by dietary sodium restriction or maintenance on control diet. At day 1, 2, 5, 7, or 50 postsectioning, immunostaining was used to detect the percentage of staining for activated macrophages, the number of αβ T cells, and the number of δγ epithelial T cells in the tongue. The number of lingual T cells did not significantly differ between treatment groups following denervation. However, there was a dramatic bilateral increase in ED1+ staining for activated macrophages in control‐fed rats that peaked at day 2 postsectioning. In contrast, sodium‐restricted rats did not show an increase in activated macrophages above baseline at any time postsectioning. Further analysis of extralingual macrophages indicated that the deficit in immune activity in sodium‐restricted rats is localized to the tongue and is not widespread. A model for immune modulation of taste receptor cell function is proposed based on these novel findings. J. Comp. Neurol. 479:43–55, 2004. © 2004 Wiley‐Liss, Inc.
Quantitative analysis of synaptic distribution along thalamocortical axons in adult mouse barrelsWhite, Edward L.; Weinfeld, Elizabeth; Lev, Dmitri L.
doi: 10.1002/cne.20300pmid: 15389615
Quantitative data on thalamocortical synapses in adult mouse barrels have been obtained largely by using lesion‐nduced degeneration to label thalamic afferents. By the time degenerating axons can be identified with the electron microscope, they have broken up into many separate pieces, making it impossible to assess the distribution of synapses along unbroken lengths of afferent. Here, this deficiency is rectified by examining intact lengths of axon labeled by the injection of biotinylated dextran amine into ipsilateral thalamus. Serial thin section reconstructions were analyzed to determine the numbers of synapses per axon length made with dendritic spines vs. shafts and the locations of synapses with respect to axonal varicosities. Results for seven axonal segments from six mice showed an average of 0.2 synapses/μm; 80% were made with spines and 20% with dendritic shafts. Just over two‐thirds of axonal varicosities formed one synapse; most of the remainder formed two and rarely three, whereas 8% formed none. Although most synapses occurred at varicosities (88%), more than 12% were made at cylindrically shaped regions of the reconstructed axonal segments. These results serve as a caveat for the use of light microscopy to quantify synapses, wherein the usual approach is to equate one varicosity with one synapse. For thalamocortical afferents to mouse barrels, equating one varicosity with one synapse would prove to be incorrect more than 30% of the time and would exclude the roughly 12% of synaptic connections made at cylindrical regions of thalamocortical afferents. J. Comp. Neurol. 479:56–69, 2004. © 2004 Wiley‐Liss, Inc.
Regulation of the CREB signaling cascade in the visual cortex by visual experience and neuronal activitySuzuki, Seigo; Al‐Noori, Salwa; Butt, Shehzad A.; Pham, Tony A.
doi: 10.1002/cne.20310pmid: 15389611
The cAMP‐responsive element (CRE) regulatory pathway has been studied as a model of signal‐regulated transcription and is critical for some forms of learning and adaptation. In cell culture systems, the extracellular‐regulated kinase (ERK) and ribosomal S6 kinase (RSK) couple synaptic signals to CRE‐mediated gene expression by modulating CRE‐binding protein (CREB) phosphorylation. However, it is not known whether sensory experience regulates gene expression in the brain by this mechanism. In this study, we ask: Are activated forms of ERK, RSK, and CREB colocalized in the cortex and are they coordinately regulated by synaptic signals? We find that these three signaling components are regulated in distinct ways. First, cells that show CRE‐lacZ reporter expression, primarily excitatory neurons, do not colocalize with cells containing phospho‐ERK. Second, while phosphorylation of ERK and RSK are modulated by visual experience, phosphorylation of CREB at serines 133, 142, or 143 is detected constitutively and is unaffected by experience. This finding suggests that neural activity might not regulate CREB phosphorylation in vivo. To test this hypothesis, we blocked action potentials by injection of tetrodotoxin and found no effect on CREB phosphorylation. These in vivo data show that, in contrast to cell culture systems, cortical synaptic activity controls CRE‐mediated gene expression without affecting CREB phosphorylation, possibly by modification of RSK and CREB‐associated coregulators. J. Comp. Neurol. 479:70–83, 2004. © 2004 Wiley‐Liss, Inc.
Calcium‐binding protein Caldendrin and CaMKII are localized in spinules of the carp retinaSchultz, Konrad; Janssen‐Bienhold, Ulrike; Gundelfinger, Eckart D.; Kreutz, Michael R.; Weiler, Reto
doi: 10.1002/cne.20314pmid: 15389610
Calcium‐binding proteins translate the influx of Ca2+ at excitatory synapses into spatiotemporal signals that regulate a variety of processes underlying synaptic plasticity. In the fish retina, the synaptic connectivity between photoreceptors and horizontal cells undergoes a remarkable plasticity, triggered by the ambient light conditions. With increasing light, the synaptic dendrites of horizontal cells form numerous spinules that are dissolved during dark adaptation. The dynamic regulation of this process is calcium‐dependent and involves the Ca2+/calmodulin‐dependent protein kinase II (CaMKII), but astonishingly its principal regulator Calmodulin (CaM) could not be localized to spinules. Here, we show that antibodies directed against Caldendrin (CaBP1), a member of the EF‐hand calcium‐binding protein family, strongly label the terminal dendrites of horizontal cells invaginating cone pedicles. Double‐labeling experiments revealed that this label is closely associated with label for CaMKII. This association was confirmed at the ultrastructural level. Caldendrin immunoreactivity and CaMKII immunoreactivity are both present in horizontal cell dendrites flanking the synaptic ribbon within the cone pedicle and in particular in spinules formed by these terminals. Comparison of light‐ and dark‐adapted retinas revealed a shift of the membrane‐associated label for Caldendrin from the terminal dendrites into the spinules during light adaptation. These results suggest that Caldendrin is involved in the dynamic regulation of spinules and confirms the assumed potential of Caldendrin as a neural calcium sensor for synaptic plasticity. J. Comp. Neurol. 479:84–93, 2004. © 2004 Wiley‐Liss, Inc.
Expression of GDNF and GFRα1 in mouse taste bud cellsTakeda, Masako; Suzuki, Yuko; Obara, Nobuko; Uchida, Nobuhiko; Kawakoshi, Kentaro
doi: 10.1002/cne.20315pmid: 15389609
GDNF (glial cell line‐derived neurotrophic factor) affects the survival and maintenance of central and peripheral neurons. Using an immunocytochemical method, we examined whether the taste bud cells in the circumvallate papillae of normal mice expressed GDNF and its GFRα1 receptor. Using double immunostaining for either of them and NCAM, PGP 9.5, or α‐gustducin, we additionally sought to determine what type of taste bud cells expressed GDNF or GFRα1, because NCAM is reported to be expressed in type‐III cells, PGP 9.5, in type‐III and some type‐II cells, and α‐gustducin, in some type‐II cells. Normal taste bud cells expressed both GDNF and GFRα1. The percentage of GDNF‐immunoreactive cells among all taste bud cells was 31.63%, and that of GFRα1‐immunoreactive cells, 83.21%. Confocal laser scanning microscopic observations after double immunostaining showed that almost none of the GDNF‐immunoreactive cells in the taste buds were reactive with anti‐NCAM or anti‐PGP 9.5 antibody, but could be stained with anti‐α‐gustducin antibody. On the other hand, almost all anti‐PGP 9.5‐ or anti‐α‐gustducin‐immunoreactive cells were positive for GFRα1. Thus, GDNF‐immunoreactive cells did not include type‐III cells, but type‐II cells, which are α‐gustducin‐immunoreactive; on the other hand, GFRα1‐immunoreactive cells included type‐II and ‐III cells, and perhaps type‐I cells. We conclude that GDNF in the type‐II cells may exert trophic actions on type‐I, ‐II, and ‐III taste bud cells by binding to their GFRα1 receptors. J. Comp. Neurol. 479:94–102, 2004. © 2004 Wiley‐Liss, Inc.
Apical‐to‐basal gradients in age‐related cochlear degeneration and their relationship to “primary” loss of cochlear neuronsOhlemiller, Kevin K.; Gagnon, Patricia M.
doi: 10.1002/cne.20326pmid: 15389608
The predominant conceptual framework for understanding human age‐related hearing loss (ARHL, or presbycusis) holds that three different cochlear elements (organ of Corti, afferent neurons, and stria vascularis) can degenerate independently, and exert independent influences on hearing. Within this framework, temporal bones from subjects with ARHL may be classified as exemplifying sensory (referring to organ of Corti), “primary” neural (loss of afferent neurons without loss of their hair cell targets), strial, or mixed ARHL. While there is general agreement as to the types of cochlear cells most affected by aging, there is less agreement about how to classify ARHL, and whether contributions of particular structures to hearing loss can be isolated. The cochlear apex of humans and animals is particularly prone to apparent primary loss of neurons that may represent an aspect of neural ARHL. We recently reported that in 129S6/SvEv mice apical neuronal loss is often accompanied by abnormalities of spiral limbus, pillar cells, and Reissner's membrane (Ohlemiller and Gagnon [2004] J Comp Neurol 469:377–390). We proposed that the initial pathology occurs within limbus, leading to disruption of perilymphatic ion homeostasis, and eventual loss of neurons as one consequence. We have now examined this issue quantitatively in young and old mice of four different strains (129S6/SvEv, CBA/J, C57BL/6, and BALB/c). Abnormalities of apical spiral limbus were found to correlate only weakly with neuronal loss. Strong correlations were found between neuronal loss and abnormalities of both pillar cells and Reissner's membrane, however. Apical neuronal loss and apical‐to‐basal progression of pathology of limbus, pillar cells, and Reissner's membrane run counter to most reported age‐related cochlear trends. Our findings suggest that these changes share a common triggering influence. J. Comp. Neurol. 479:103–116, 2004. © 2004 Wiley‐Liss, Inc.