bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three‐dimensional synaptic ultrastructure in the dentate gyrus and hippocampal area CA3 in the Ts65Dn mouse model of down syndrome
Authors: Popov Victor I. , Kleschevnikov Alexander M. , Klimenko Oleg A. , Stewart Michael G. , Belichenko Pavel V. 
Published: December 2010

AbstractDown syndrome (DS) results from trisomy of human chromosome 21. Ts65Dn mice are an established model for DS and show several phenotypes similar to those in people with DS. However, there is little data on the structural plasticity of synapses in the trisynaptic pathway in the hippocampus. Here we investigate 3D ultrastructure of synapses in the hippocampus of age‐matched control (2N) and Ts65Dn male mice. Serial ultrathin sections and 3D reconstructions characterize synapses in the middle molecular layer (MML) of dentate gyrus and in thorny excrescences (TEs) in proximal portions of apical dendrites of CA3 pyramidal neurons. 3D analysis of synapses shows phenotypes that distinguish Ts65Dn from 2N mice. For the MML, synapse density was reduced by 15% in Ts65Dn vs. 2N mice (P < 0.05). Comparative 3D analyses demonstrate a significant decrease in the number of thorns per TE in CA3 in Ts65Dn vs. 2N mice (by ≈45%, P = 0.01). Individual thorn volume was 3 times smaller in Ts65Dn vs. 2N mice (P = 0.02). A significant decrease in the number of thorn projections per TE in Ts65Dn vs. 2N mice was accompanied by a decrease of filopodium‐like protrusions on the surface of TEs (P = 0.02). However, the volume of postsynaptic densities in CA3 Ts65Dn and 2N mice was unchanged (P = 0.78). Our findings suggest that the high degree of plasticity of CA3 thorns may be connected with their filopodial origin. Alterations of 3D synaptic structure in Ts65Dn mice may further contribute to the diminished plasticity in DS. J. Comp. Neurol. 519:1338–1354, 2011. © 2010 Wiley‐Liss, Inc.
Calcium‐binding protein distributions and fiber connections of the nucleus accumbens in the pigeon (columba livia)
Authors: Husband Scott A. , Shimizu Toru 
Published: December 2010

AbstractUntil recently, the exact location of the avian nucleus accumbens within the basal forebrain had not been well established (Reiner et al. [2004] J Comp Neurol 473:377–414). While a number of previous studies have shown afferents and efferents of the presumptive “nucleus accumbens,” detailed and accurate connection patterns of this newly recognized area are still lacking. We set out to clarify these connections using small, localized injections of cholera toxin subunit B and biotinylated dextran amine directly into the nucleus. In order to increase the accuracy of tracer injections into target sites, we first conducted a systematic comparison of three calcium‐binding proteins, namely, parvalbumin, calretinin, and calbindin, to characterize the nucleus accumbens and ascertain its boundaries. The results showed that the avian and mammalian nucleus accumbens had remarkable hodological similarities, including the connections with the hippocampus, amygdala, ventral pallidum, lateral hypothalamus, and ventral tegmental area. However, the most significant aspect of the present study is that the avian nucleus accumbens had extensive reciprocal connections with medial pallial structures, the mammalian counterparts of which are unclear. Three implications of this finding are discussed. First, the avian medial pallium may correspond to part of the mammalian prefrontal cortex based on the connections with the nucleus accumbens. Second, the avian brain has a “limbic loop” involving the medial pallium, which also receives input from the avian equivalent of the mediodorsal thalamus. Third, the extensive connections between the accumbens and medial pallium just dorsal to it suggest a column‐like organization of limbic‐associated areas in the avian telencephalon. J. Comp. Neurol. 519:1371–1394, 2011. © 2010 Wiley‐Liss, Inc.
Synaptic proteins are tonotopically graded in postnatal and adult type I and type II spiral ganglion neurons
Authors: Flores‐Otero Jacqueline , Davis Robin L. 
Published: December 2010

AbstractInherent in the design of the mammalian auditory system is the precision necessary to transduce complex sounds and transmit the resulting electrical signals to higher neural centers. Unique specializations in the organ of Corti are required to make this conversion, such that mechanical and electrical properties of hair cell receptors are tailored to their specific role in signal coding. Electrophysiological and immunocytochemical characterizations have shown that this principle also applies to neurons of the spiral ganglion, as evidenced by distinctly different firing features and synaptic protein distributions of neurons that innervate high‐ and low‐frequency regions of the cochlea. However, understanding the fine structure of how these properties are distributed along the cochlear partition and within the type I and type II classes of spiral ganglion neurons is necessary to appreciate their functional significance fully. To address this issue, we assessed the localization of the postsynaptic AMPA receptor subunits GluR2 and GluR3 and the presynaptic protein synaptophysin by using immunocytochemical labeling in both postnatal and adult tissue. We report that these presynaptic and postsynaptic proteins are distributed oppositely in relation to the tonotopic map and that they are equally distributed in each neuronal class, thus having an overall gradation from one end of the cochlea to the other. For synaptophysin, an additional layer of heterogeneity was superimposed orthogonal to the tonotopic axis. The highest anti‐synaptophysin antibody levels were observed within neurons located close to the scala tympani compared with those located close to the scala vestibuli. Furthermore, we noted that the protein distribution patterns observed in postnatal preparations were largely retained in adult tissue sections, indicating that these features characterize spiral ganglion neurons in the fully developed ear. J. Comp. Neurol. 519:1455–1475, 2011. © 2010 Wiley‐Liss, Inc.
Neurogliaform cells in the molecular layer of the dentate gyrus as feed‐forward γ‐aminobutyric acidergic modulators of entorhinal–hippocampal interplay
Authors: Armstrong Caren , Szabadics János , Tamás Gábor , Soltesz Ivan 
Published: December 2010

AbstractFeed‐forward inhibition from molecular layer interneurons onto granule cells (GCs) in the dentate gyrus is thought to have major effects regulating entorhinal–hippocampal interactions, but the precise identity, properties, and functional connectivity of the GABAergic cells in the molecular layer are not well understood. We used single and paired intracellular patch clamp recordings from post‐hoc‐identified cells in acute rat hippocampal slices and identified a subpopulation of molecular layer interneurons that expressed immunocytochemical markers present in members of the neurogliaform cell (NGFC) class. Single NGFCs displayed small dendritic trees, and their characteristically dense axonal arborizations covered significant portions of the outer and middle one‐thirds of the molecular layer, with frequent axonal projections across the fissure into the CA1 and subicular regions. Typical NGFCs exhibited a late firing pattern with a ramp in membrane potential prior to firing action potentials, and single spikes in NGFCs evoked biphasic, prolonged GABAA and GABAB postsynaptic responses in GCs. In addition to providing dendritic GABAergic inputs to GCs, NGFCs also formed chemical synapses and gap junctions with various molecular layer interneurons, including other NGFCs. NGFCs received low‐frequency spontaneous synaptic events, and stimulation of perforant path fibers revealed direct, facilitating synaptic inputs from the entorhinal cortex. Taken together, these results indicate that NGFCs form an integral part of the local molecular layer microcircuitry generating feed‐forward inhibition and provide a direct GABAergic pathway linking the dentate gyrus to the CA1 and subicular regions through the hippocampal fissure. J. Comp. Neurol. 519:1476–1491, 2011. © 2010 Wiley‐Liss, Inc.
Patterns of axonal collateralization of single layer V cortical projection neurons in the rat presubiculum
Authors: Honda Yoshiko , Furuta Takahiro , Kaneko Takeshi , Shibata Hideshi , Sasaki Hiroshi 
Published: December 2010

AbstractThe presubiculum is one of the important regions of the parahippocampal area known to be responsible for processing and integrating spatial representation information. To understand better the functional roles played by the presubiculum, it is essential to elucidate how output signals from the presubiculum distribute to its target regions. In the present study, the axonal branching patterns of single pyramidal neurons in layer V of the rat presubiculum were investigated by using in vivo injection of a viral vector expressing membrane‐targeted palmitoylation site‐attached green fluorescent protein. We found that individual layer V neurons provide axonal branches to one or two cortical areas with one or more recurrent collaterals to the presubiculum. These neurons were classified into six types, based on their axonal collateralization pattern: neurons with axon branches to 1) both the retrosplenial granular cortex and the parasubiculum, 2) both the retrosplenial granular cortex and the subiculum, and 3) both the medial entorhinal area and the subiculum, and neurons with axonal branches terminating only in 4) the retrosplenial granular cortex, 5) the subiculum, and 6) the presubiculum. Types 1–5 also provide recurrent axons to the presubiculum. Our data demonstrate that layer V of the presubiculum consists of at least six types of cortical projection neurons with various patterns of axonal collateralization. These findings suggest that single presubicular layer V neurons may distribute information to one or two cortical areas participating in the neural circuitry of spatial representation and also send such information back to the presubiculum itself. J. Comp. Neurol. 519:1395–1412, 2011. © 2010 Wiley‐Liss, Inc.
Structure and function of bistratified intrinsically photosensitive retinal ganglion cells in the mouse
Authors: Schmidt Tiffany M. , Kofuji Paulo 
Published: December 2010

AbstractA subpopulation of retinal ganglion cells (RGCs) expresses the photopigment melanopsin, rendering these cells intrinsically photosensitive (ipRGCs). These cells are critical for competent circadian entrainment, pupillary light reflex, and other non‐imaging‐forming photic responses. Research has now demonstrated the presence of multiple subpopulations of ipRGC based on the dendritic stratification in the inner plexiform layer (IPL), those monostratified in the Off sublamina (M1), those monostratified in the On sublamina (M2,4,5), and those bistratified in both the On and the Off sublaminae (M3). Despite evidence that M1 and M2 cells are distinct subpopulations of ipRGC based on distinct morphological and physiological properties, the inclusion of M3 cells as a distinct subtype has remained controversial. Aside from the identification of M3 cells as a morphological subpopulation of ipRGC, to date there have been no functional descriptions of M3 cell physiology or synaptic inputs. Our data provide the first in‐depth description of M3 cell structural and functional properties. We report that M3 cells form a morphologically heterogeneous population but one that is physiologically homogeneous with properties similar to those of M2 cells. J. Comp. Neurol. 519:1492–1504, 2011. © 2010 Wiley‐Liss, Inc.
Brain‐derived neurotrophic factor promotes cochlear spiral ganglion cell survival and function in deafened, developing cats
Authors: Leake Patricia A. , Hradek Gary T. , Hetherington Alexander M. , Stakhovskaya Olga 
Published: December 2010

AbstractPostnatal development and survival of spiral ganglion (SG) neurons depend on both neural activity and neurotrophic support. Our previous studies showed that electrical stimulation from a cochlear implant only partially prevents SG degeneration after early deafness. Thus, neurotrophic agents that might be combined with an implant to improve neural survival are of interest. Recent studies reporting that brain‐derived neurotrophic factor (BDNF) promotes SG survival after deafness have been conducted in rodents and limited to relatively short durations. Our study examined longer duration BDNF treatment in deafened cats that may better model the slow progression of SG degeneration in human cochleae, and this is the first study of BDNF in the developing auditory system. Kittens were deafened neonatally, implanted at 4–5 weeks with intracochlear electrodes containing a drug‐delivery cannula, and BDNF or artificial perilymph was infused for 10 weeks from a miniosmotic pump. In BDNF‐treated cochleae, SG cells grew to normal size and were significantly larger than cells on the contralateral side. However, their morphology was not completely normal, and many neurons lacked or had thinned perikaryl myelin. Unbiased stereology was employed to estimate SG cell density, independent of cell size. BDNF was effective in promoting significantly improved survival of SG neurons in these developing animals. BDNF treatment also resulted in higher density and larger size of myelinated radial nerve fibers, sprouting of fibers into the scala tympani, and improvement of electrically evoked auditory brainstem response thresholds. BDNF may have potential therapeutic value in the developing auditory system, but many serious obstacles currently preclude clinical application. J. Comp. Neurol. 519:1526–1545, 2011. © 2010 Wiley‐Liss, Inc.
A specific antibody to neuropeptide AF1 (KNEFIRFamide) recognizes a small subset of neurons in Ascaris suum: differences from Caenorhabditis elegans
Authors: Sithigorngul Paisarn , Jarecki Jessica L. , Stretton Antony O.W. 
Published: December 2010

AbstractA monoclonal antibody, AF1‐003, highly specific to the Ascaris suum neuropeptide AF1 (KNEFIRFamide), was generated. This antibody binds strongly to AF1 and extremely weakly to other peptides with C‐terminal FIRFamide: AF5 (SGKPTFIRFamide), AF6 (FIRFamide), and AF7 (AGPRFIRFamide). It does not recognize 35 other AF (A. suum FMRFamide‐like) peptides at the highest concentration tested, nor does it recognize FMRFamide. When crude peptide extracts of A. suum are fractionated by two‐step HPLC, the only fractions recognized by AF1‐003 are those comigrating with synthetic AF1. By immunocytochemistry, antibody AF1‐003 recognizes a small subset of the 298 neurons of A. suum: these include the paired URX and RIP neurons, two pairs of lateral ganglion neurons in the head, and the unpaired PQR and PDA or ‐B tail neurons that send processes to the head along the dorsal and ventral nerve cords, respectively. AF1 immunoreactivity is also seen in three pairs of pharyngeal neurons. Mass spectroscopy (MS) shows the presence of AF1 in the head, pharynx, and dorsal and ventral nerve cords. In A. suum, the neurons that contain AF1 show little overlap with neurons that express green fluorescent protein constructs targeting the flp‐8 gene, which encodes AF1 in Caenorhabditis elegans (Kim and Li [2004] J. Comp. Neurol. 475:540–550); the URX neurons express AF1 in both species, but, in C. elegans, flp‐8 expression was not detected in RIP, PQR, and PDA or ‐B or in the pharynx. Other, less specific monoclonal antibodies recognize AF1, as well as other peptides to differing degrees; these antibodies are useful reagents for determination of neuronal morphology. J. Comp. Neurol. 519:1546–1561, 2011. © 2010 Wiley‐Liss, Inc.
Formation of the spinal network in zebrafish determined by domain‐specific pax genes
Authors: Ikenaga Takanori , Urban Jason M. , Gebhart Nichole , Hatta Kohei , Kawakami Koichi , Ono Fumihito 
Published: December 2010

AbstractIn the formation of the spinal network, various transcription factors interact to develop specific cell types. By using a gene trap technique, we established a stable line of zebrafish in which the red fluorescent protein (RFP) was inserted into the pax8 gene. RFP insertion marked putative pax8‐lineage cells with fluorescence and inhibited pax8 expression in homozygous embryos. Pax8 homozygous embryos displayed defects in the otic vesicle, as previously reported in studies with morpholinos. The pax8 homozygous embryos survived to adulthood, in contrast to mammalian counterparts that die prematurely. RFP is expressed in the dorsal spinal cord. Examination of the axon morphology revealed that RFP+ neurons include commissural bifurcating longitudinal (CoBL) interneurons, but other inhibitory neurons such as commissural local (CoLo) interneurons and circumferential ascending (CiA) interneurons do not express RFP. We examined the effect of inhibiting pax2a/pax8 expression on interneuron development. In pax8 homozygous fish, the RFP+ cells underwent differentiation similar to that of pax8 heterozygous fish, and the swimming behavior remained intact. In contrast, the RFP+ cells of pax2a/pax8 double mutants displayed altered cell fates. CoBLs were not observed. Instead, RFP+ cells exhibited axons descending ipsilaterally, a morphology resembling that of V2a/V2b interneurons. J. Comp. Neurol. 519:1562–1579, 2011. © 2010 Wiley‐Liss, Inc.
Synaptic inputs to two types of koniocellular pathway ganglion cells in marmoset retina
Authors: Percival Kumiko A. , Martin Paul R. , Grünert Ulrike 
Published: December 2010

AbstractThe retinal connectivity of the diverse group of cells contributing to koniocellular visual pathways (widefield ganglion cells) is largely unexplored. Here we examined the synaptic inputs onto two koniocellular‐projecting ganglion cell types named large sparse and broad thorny cells. Ganglion cells were labeled by retrograde tracer injections targeted to koniocellular layer K3 in the lateral geniculate nucleus in marmosets (Callithrix jacchus) and subsequently photofilled. Retinal preparations were processed with antibodies against the C‐terminal binding protein 2, the AMPA receptor subunit GluR4, and against CD15 to identify bipolar (excitatory) and/or antibodies against gephyrin to identify amacrine (inhibitory) input. Large sparse cells are narrowly stratified close to the ganglion cell layer. Broad thorny ganglion cells are broadly stratified in the center of the inner plexiform layer. Bipolar input to large sparse cells derives from DB6 and maybe other ON bipolar types, whereas that to broad thorny cells derives from ON and OFF bipolar cell types. The total number of putative synapses on broad thorny cells is higher than the number on large sparse cells but the density of inputs (between 2 and 5 synapses per 100 μm2 dendritic area) is similar for the two cell types, indicating that the larger number of synapses on broad thorny cells is attributable to the larger membrane surface area of this cell type. Synaptic input density is comparable to previous values for midget‐parvocellular and parasol‐magnocellular pathway cells. This suggests functional differences between koniocellular, parvocellular, and magnocellular pathways do not arise from variation in synaptic input densities. J. Comp. Neurol. 519:2135–2153, 2011. © 2010 Wiley‐Liss, Inc.
Major isoform of zebrafish P0 is a 23.5 kDa myelin glycoprotein expressed in selected white matter tracts of the central nervous system
Authors: Bai Qing , Sun Ming , Stolz Donna B. , Burton Edward A. 
Published: December 2010

AbstractThe zebrafish mpz gene, encoding the ortholog of mammalian myelin protein zero, is expressed in oligodendrocytes of the zebrafish central nervous system (CNS). The putative gene product, P0, has been implicated in promoting axonal regeneration in addition to its proposed structural functions in compact myelin. We raised novel zebrafish P0‐specific antibodies and established that P0 is a 23.5 kDa glycoprotein containing a 3 kDa N‐linked carbohydrate moiety. P0 was localized to myelin sheaths surrounding axons, but was not detected in the cell bodies or proximal processes of oligodendrocytes. Many white matter tracts in the adult zebrafish CNS were robustly immunoreactive for P0, including afferent visual and olfactory pathways, commissural and longitudinal tracts of the brain, and selected ascending and descending tracts of the spinal cord. P0 was first detected during development in premyelinating oligodendrocytes of the ventral hindbrain at 48 hours postfertilization (hpf). By 72 hpf, short segments of longitudinally oriented P0‐immunoreactive myelinating axons were seen in the hindbrain; expression in the spinal cord, optic pathways, hindbrain commissures, midbrain, and peripheral nervous system followed. The mpz transcript was found to be alternatively spliced, giving rise to P0 isoforms with alternative C‐termini. The 23.5 kDa isoform was most abundant in the CNS, but other isoforms predominated in the myelin sheath surrounding the Mauthner axon. These data provide a detailed account of P0 expression and demonstrate novel P0 isoforms, which may have discrete functional properties. The restriction of P0 immunoreactivity to myelin sheaths indicates that the protein is subject to stringent intracellular compartmentalization, which likely occurs through posttranslational mechanisms. J. Comp. Neurol. 519:1580–1596, 2011. © 2010 Wiley‐Liss, Inc.
Increase of close homolog of cell adhesion molecule L1 in primary afferent by nerve injury and the contribution to neuropathic pain
Authors: Yamanaka Hiroki , Kobayashi Kimiko , Okubo Masamichi , Fukuoka Tetsuo , Noguchi Koichi 
Published: December 2010

AbstractThe L1 family of cell adhesion molecules (L1‐CAMs) is known to be involved in various neuronal functions such as cell adhesion, axon guidance, and synaptic plasticity. We investigated the detailed expression/changes of a close homolog of the L1 cell adhesion molecule (CHL1) after nerve injury and the possible role on neuropathic pain using the rat spared nerve injury (SNI) model. SNI induced the expression of CHL1 in L4/5 DRG neurons, particularly in small‐size injured neurons and in satellite cells. In the spinal cord, CHL1 immunoreactivity increased mainly in laminae I–II of the dorsal horn on the side ipsilateral to the nerve injury. Ultrastructural study clarified the fine localization of CHL1 in axons of primary afferents in the dorsal horn. CHL1 immunoreactivities were localized in the adherence such as axon–axon, axon–dorsal horn neurons (dendrite, soma), and axon–glial cells (astrocyte and microglia). Experimental inhibition of CHL1 adhesion by intrathecal administration of the antibody for CHL1 extracellular domain significantly prevented and reversed SNI‐induced mechanical allodynia. Thus, alterations of CHL1 may be involved in the structural plasticity after peripheral nerve injury and have important roles in neuropathic pain. J. Comp. Neurol. 519:1597–1615, 2011. © 2010 Wiley‐Liss, Inc.