pinecone/core-2020-05-10-deduplication huggingface dataset:
Septal projections to the nucleus incertus in the rat: Bidirectional pathways for modulation of hippocampal function

Projections from the nucleus incertus (NI) to the septum have been implicated in the modulation of hippocampal theta rhythm. In this study we describe a previously uncharacterized projection from the septum to the NI, which may provide feedback modulation of the ascending circuitry. Fluorogold injections into the NI resulted in retrograde labeling in the septum that was concentrated in the horizontal diagonal band and areas of the posterior septum including the septofimbrial and triangular septal nuclei. Double-immunofluorescent staining indicated that the majority of NI-projecting septal neurons were calretinin-positive and some were parvalbumin-, calbindin-, or glutamic acid decarboxylase (GAD)−67-positive. Choline acetyltransferase-positive neurons were Fluorogold-negative. Injection of anterograde tracers into medial septum, or triangular septal and septofimbrial nuclei, revealed fibers descending to the supramammillary nucleus, median raphe, and the NI. These anterogradely labeled varicosities displayed synaptophysin immunoreactivity, indicating septal inputs form synapses on NI neurons. Anterograde tracer also colocalized with GAD-67-positive puncta in labeled fibers, which in some cases made close synaptic contact with GAD-67-labeled NI neurons. These data provide evidence for the existence of an inhibitory descending projection from medial and posterior septum to the NI that provides a "feedback loop" to modulate the comparatively more dense ascending NI projections to medial septum and hippocampus. Neural processes and associated behaviors activated or modulated by changes in hippocampal theta rhythm may depend on reciprocal connections between ascending and descending pathways rather than on unidirectional regulation via the medial septum.Grant sponsors: Fundación Alicia Koplowitz Fellowship (to A.M.S.P.), CAPES-Brasil Bex - 4494/09-1 (to F.N.S.) and 4496/09-4 (to C.W.P.) and Fapitec edital #01/08 (to F.N.S.), FIS-isciiiPI10/01399 (to J.S.), National Health and Medical Research Council of Australia - 520299 (to S.M.), 509246, 1005985, and 1005988 (to A.L.G.), the Florey Foundation (to S.M., A.L.G.), Besen Family Foundation (to A.L.G.) and a NEUREN project, FP7-PEOPLE-IRSES PIRSES-GA-2012-318997 (to A.L.G., F.E.O.-B.)
Ultrastructure of the Odontocete Organ of Corti: Scanning and Transmission Electron Microscopy

The morphological study of the Odontocete organ of Corti, together with possible alterations associated with damage from sound exposure, represents a key conservation approach to assess the effects of acoustic pollution on marine ecosystems. By collaborating with stranding networks from several European countries, 150 ears from 13 species of Odontocetes were collected and analyzed by scanning (SEM) and transmission (TEM) electron microscopy. Based on our analyses, we first describe and compare Odontocete cochlear structures and then propose a diagnostic method to identify inner ear alterations in stranded individuals. The two species analyzed by TEM (Phocoena phocoena and Stenella coeruleoalba) showed morphological characteristics in the lower basal turn of high-frequency hearing species. Among other striking features, outer hair cell bodies were extremely small and were strongly attached to Deiters cells. Such morphological characteristics, shared with horseshoe bats, suggest that there has been convergent evolution of sound reception mechanisms among echolocating species. Despite possible autolytic artifacts due to technical and experimental constraints, the SEM analysis allowed us to detect the presence of scarring processes resulting from the disappearance of outer hair cells from the epithelium. In addition, in contrast to the rapid decomposition process of the sensory epithelium after death (especially of the inner hair cells), the tectorial membrane appeared to be more resistant to postmortem autolysis effects. Analysis of the stereocilia imprint pattern at the undersurface of the tectorial membrane may provide a way to detect possible ultrastructural alterations of the hair cell stereocilia by mirroring them on the tectorial membrane. J. Comp. Neurol. 523:431-448, 2015. (c) 2014 Wiley Periodicals, Inc.Postprint (published version
Olfactory ensheathing cells are the main phagocytic cells that remove axon debris during early development of the olfactory system

During development of the primary olfactory system, axon targeting is inaccurate and axons inappropriately project within the target layer or over-project into the deeper layers of the olfactory bulb. As a consequence there is considerable apoptosis of primary olfactory neurons during embryonic and postnatal development and axons of the degraded neurons need to be removed. Olfactory ensheathing cells (OECs) are the glia of the primary olfactory nerve and are known to phagocytose axon debris in the adult and postnatal animal. However it is unclear when phagocytosis by OECs first commences. We have investigated the onset of phagocytosis by OECs in the developing mouse olfactory system by utilizing two transgenic reporter lines: OMP-ZsGreen mice which express bright green fluorescent protein in primary olfactory neurons and S100߭DsRed mice which express red fluorescent protein in OECs. In crosses of these mice, the fate of the degraded axon debris is easily visualized. We found evidence of axon degradation at E13.5. Phagocytosis of the primary olfactory axon debris by OECs was first detected at E14.5. Phagocytosis of axon debris continued into the postnatal animal during the period when there was extensive mis-targeting of olfactory axons. Macrophages were often present in close proximity to OECs but they contributed only a minor role to clearing the axon debris, even after widespread degeneration of olfactory neurons by unilateral bulbectomy and methimazole treatment. These results demonstrate that from early in embryonic development OECs are the primary phagocytic cells of the primary olfactory nerve.Full Tex
Neurochemical characterization of extrinsic nerves in myenteric ganglia of the guinea pig distal colon

"This is the peer reviewed version of the following article: [Chen, B. N., Sharrad, D. F., Hibberd, T. J., Zagorodnyuk, V. P., Costa, M. and Brookes, S. J.H. (2015), Neurochemical characterization of extrinsic nerves in myenteric ganglia of the guinea pig distal colon. J. Comp. Neurol., 523: 742–756. doi: 10.1002/cne.23704], which has been published in final form at [http://dx.doi.org/10.1002/cne.23704]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. http://olabout.wiley.com/WileyCDA/Section/id-820227.html#terms"Extrinsic nerves to the gut influence the absorption of water and electrolytes and expulsion of waste contents, largely via regulation of enteric neural circuits; they also contribute to the control of blood flow. The distal colon is innervated by extrinsic sympathetic and parasympathetic efferent and spinal afferent neurons, via axons in colonic nerve trunks. In the present study, biotinamide tracing of colonic nerves was combined with immunohistochemical labeling for markers of sympathetic, parasympathetic and spinal afferent neurons to quantify their relative contribution to the extrinsic innervation. Calcitonin gene-related peptide, vesicular acetylcholine transporter and tyrosine hydroxylase, which selectively label spinal afferent, parasympathetic and sympathetic axons, respectively, were detected immunohistochemically in 1 ± 0.5% (n = 7), 15 ± 4.7% (n = 6) and 24 ± 4% (n = 7) of biotinamide-labeled extrinsic axons in myenteric ganglia. Immunoreactivity for vasoactive intestinal polypeptide, nitric oxide synthase, somatostatin, vesicular glutamate transporters 1 and 2 accounted for a combined maximum of 14% of biotinamide-labeled axons in myenteric ganglia. Thus, a maximum of 53% of biotinamide-labeled extrinsic axons in myenteric ganglia were labeled by antisera to one of these eight markers. Viscerofugal neurons were also labeled by biotinamide, and shown to have distinct morphologies and spatial distributions that correlated closely with their immunoreactivity for nitric oxide synthase and choline acetyltransferase. As reported for the rectum, nearly half of all extrinsic nerve fibers to the distal colon lack the key immunohistochemical markers commonly used for their identification. Their abundance may therefore have been significantly underestimated in previous immunohistochemical studies
Brain Composition in Godyris zavaleta, a Diurnal Butterfly, Reflects an Increased Reliance on Olfactory Information

Interspecific comparisons of brain structure can inform our functional understanding of brain regions, identify adaptations to species-specific ecologies, and explore what constrains adaptive changes in brain structure, and coevolution between functionally related structures. The value of such comparisons is enhanced when the species considered have known ecological differences. The Lepidoptera have long been a favored model in evolutionary biology, but to date descriptions of brain anatomy have largely focused on a few commonly used neurobiological model species. We describe the brain of Godyris zavaleta (Ithomiinae), a member of a subfamily of Neotropical butterflies with enhanced reliance on olfactory information. We demonstrate for the first time the presence of sexually dimorphic glomeruli within a distinct macroglomerular complex (MGC) in the antennal lobe of a diurnal butterfly. This presents a striking convergence with the well-known moth MGC, prompting a discussion of the potential mechanisms behind the independent evolution of specialized glomeruli. Interspecific analyses across four Lepidoptera further show that the relative size of sensory neuropils closely mirror interspecific variation in sensory ecology, with G. zavaleta displaying levels of sensory investment intermediate between the diurnal monarch butterfly (Danaus plexippus), which invests heavily in visual neuropil, and night-flying moths, which invest more in olfactory neuropil. We identify several traits that distinguish butterflies from moths, and several that distinguish D. plexippus and G. zavaleta. Our results illustrate that ecological selection pressures mold the structure of invertebrate brains, and exemplify how comparative analyses across ecologically divergent species can illuminate the functional significance of variation in brain structure.Peer-reviewedPublisher Versio
Dendrodendritic synapses in the mouse olfactory bulb external plexiform layer

Odor information relayed by olfactory bulb projection neurons, mitral and tufted cells (M/T), is modulated by pairs of reciprocal dendrodendritic synaptic circuits in the external plexiform layer (EPL). Interneurons, which are accounted for largely by granule cells, receive depolarizing input from M/T dendrites and in turn inhibit current spread in M/T dendrites via hyperpolarizing reciprocal dendrodendritic synapses. Because the location of dendrodendritic synapses may significantly affect the cascade of odor information, we assessed synaptic properties and density within sublaminae of the EPL and along the length of M/T secondary dendrites. In electron micrographs the M/T to granule cell synapse appeared to predominate and was equivalent in both the outer and inner EPL. However, the dendrodendritic synapses from granule cell spines onto M/T dendrites were more prevalent in the outer EPL. In contrast, individual gephyrin-immunoreactive (IR) puncta, a postsynaptic scaffolding protein at inhibitory synapses used here as a proxy for the granule to M/T dendritic synapse was equally distributed throughout the EPL. Of significance to the organization of intrabulbar circuits, gephyrin-IR synapses are not uniformly distributed along M/T secondary dendrites. Synaptic density, expressed as a function of surface area, increases distal to the cell body. Furthermore, the distributions of gephyrin-IR puncta are heterogeneous and appear as clusters along the length of the M/T dendrites. Consistent with computational models, our data suggest that temporal coding in M/T cells is achieved by precisely located inhibitory input and that distance from the soma is compensated for by an increase in synaptic density.Fil: Bartel, Dianna L.. University Of Yale. School Of Medicine; Estados UnidosFil: Rela, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Hsieh, Lawrence. University Of Yale. School Of Medicine; Estados UnidosFil: Greer, Charles A. . University Of Yale. School Of Medicine; Estados Unido
Chronic pain and arthritis – studies of mechanisms in the regulation of hypersensitivity

Chronic pain is one of the most devastating symptoms reported by rheumatoid arthritis (RA) patients. Current treatment strategies are focusing on dampening the inflammatory and immunological aspects of RA, but unfortunately subgroups of patients continue to suffer from pain, even when the disease is adequately controlled. In this thesis, the work is focused on investigating mechanisms underlying arthritis-induced pain using the collagen antibody-induced arthritis mouse (CAIA) model.



In Paper I, we describe 50 peptides that are only expressed, and 38 peptides that are predominantly expressed in the dorsal spinal cord using liquid chromatography mass spectrometry. Intrathecal injection of [des-Ser1]-cerebellin (desCER), one of the peptides predominantly expressed in the spinal dorsal horn, induces a dose-dependent mechanical hypersensitivity but has no effect on thermal sensitivity in mice. We also show that the precursor of desCER is expressed in excitatory interneurons of laminae II/III. This study suggests that desCER is a novel pain modulator, and provides a platform for continued exploration of novel neuropeptides involved in nociception.



In Paper II, we report that mice subjected to CAIA display transient inflammation and persistent mechanical hypersensitivity. We find an anti-nociceptive effect of a COX inhibitor, but only in the inflammatory phase of the CAIA model, and a time-dependent spinal glial activation.



In Paper III, we report neurochemical changes in dorsal root ganglia (DRGs) and spinal cord after induction of CAIA. In the CAIA DRGs, galanin, voltage-gated calcium channel subunit α2δ1 and the nerve injury markers ATF3 and GAP43 are up-regulated. Taken together, based on the pharmacological and neurochemical profile, our work suggests that antibody-driven joint inflammation lead to a partial neuropathic pain phenotype.



Finally, in Paper IV we focus on the role of lysophosphatidic acid (LPA) in arthritis-induced pain. The LPA synthesizing enzyme autotaxin is increased in DRGs from mice subjected to CAIA. Systemic treatment with a monoclonal antibody (Ab) against LPA completely reverses arthritis-induced mechanical and thermal pain-like behavior and also blocks the up- regulation of α2δ1 in peripheral sensory neurons of CAIA mice. We also find that the expression of α2δ1 remains at basal levels in Lpa receptor-1 (Lpar1) deficient CAIA mice. These results provide new insights into the role of the LPA1/α2δ1 axis in arthritis-induced pain, suggesting new potential therapeutic targets for pain relief in RA.



In summary, we have described a battery of pain-related factors involved in CAIA-induced hypersensitivity. These results lead to a deeper understanding of pain mechanisms in RA and hopefully to new therapeutic approaches to treat the pain component in RA patients
Vesicular stomatitis virus enables gene transfer and transsynaptic tracing in a wide range of organisms

Current limitations in technology have prevented an extensive analysis of the connections among neurons, particularly within nonmammalian organisms. We developed a transsynaptic viral tracer originally for use in mice, and then tested its utility in a broader range of organisms. By engineering the vesicular stomatitis virus (VSV) to encode a fluorophore and either the rabies virus glycoprotein (RABV-G) or its own glycoprotein (VSV-G), we created viruses that can transsynaptically label neuronal circuits in either the retrograde or anterograde direction, respectively. The vectors were investigated for their utility as polysynaptic tracers of chicken and zebrafish visual pathways. They showed patterns of connectivity consistent with previously characterized visual system connections, and revealed several potentially novel connections. Further, these vectors were shown to infect neurons in several other vertebrates, including Old and New World monkeys, seahorses, axolotls, and Xenopus. They were also shown to infect two invertebrates, Drosophila melanogaster, and the box jellyfish, Tripedalia cystophora, a species previously intractable for gene transfer, although no clear evidence of transsynaptic spread was observed in these species. These vectors provide a starting point for transsynaptic tracing in most vertebrates, and are also excellent candidates for gene transfer in organisms that have been refractory to other methods
Postsynaptic gephyrin clustering controls the development of adult-born granule cells in the olfactory bulb

In adult rodent olfactory bulb, GABAergic signaling regulates migration, differentiation, and synaptic integration of newborn granule cells (GCs), migrating from the subventricular zone. Here we show that these effects depend on the formation of a postsynaptic scaffold organized by gephyrin-the main scaffolding protein of GABAergic synapses, which anchors receptors and signaling molecules to the postsynaptic density-and are regulated by the phosphorylation status of gephyrin. Using lentiviral vectors to selectively transfect adult-born GCs, we observed that overexpression of the phospho-deficient gephyrin mutant eGFP-gephyrin(S270A), which facilitates the formation of supernumerary GABAergic synapses in vitro, favors dendritic branching and the formation of transient GABAergic synapses on spines, identified by the presence of α2-GABAA Rs. In contrast, overexpression of the dominant-negative eGFP-gephyrin(L2B) (a chimera that is enzymatically active but clustering defective), curtailed dendritic growth, spine formation, and long-term survival of GCs, pointing to the essential role of gephyrin cluster formation for its function. We could exclude any gephyrin overexpression artifacts, as GCs infected with eGFP-gephyrin were comparable to those infected with eGFP alone. The opposite effects induced by the two gephyrin mutant constructs indicate that the gephyrin scaffold at GABAergic synapses orchestrates signaling cascades acting on the cytoskeleton to regulate neuronal growth and synapse formation. Specifically, gephyrin phosphorylation emerges as a novel mechanism regulating morphological differentiation and long-term survival of adult-born olfactory bulb neurons
Sociality and the telencephalic distribution of corticotrophin-releasing factor, urocortin 3, and binding sites for CRF type 1 and type 2 receptors : a comparative study of eusocial naked mole-rats and solitary Cape mole-rats

Various aspects of social behavior are influenced by the
highly conserved corticotrophin-releasing factor (CRF)
family of peptides and receptors in the mammalian telencephalon.
This study has mapped and compared the telencephalic
distribution of the CRF receptors, CRF1 and
CRF2, and two of their ligands, CRF and urocortin 3,
respectively, in African mole-rat species with diametrically
opposed social behavior. Naked mole-rats live in large
eusocial colonies that are characterized by exceptional
levels of social cohesion, tolerance, and cooperation in
burrowing, foraging, defense, and alloparental care for the
offspring of the single reproductive female. Cape molerats
are solitary; they tolerate conspecifics only fleetingly
during the breeding season. The telencephalic sites at
which the level of CRF1 binding in naked mole-rats
exceeds that in Cape mole-rats include the basolateral amygdaloid nucleus, hippocampal CA3 subfield, and dentate
gyrus; in contrast, the level is greater in Cape molerats
in the shell of the nucleus accumbens and medial
habenular nucleus. For CRF2 binding, the sites with a
greater level in naked mole-rats include the basolateral
amygdaloid nucleus and dentate gyrus, but the septohippocampal
nucleus, lateral septal nuclei, amygdalostriatal
transition area, bed nucleus of the stria terminalis, and
medial habenular nucleus display a greater level in Cape
mole-rats. The results are discussed with reference to
neuroanatomical and behavioral studies of various species,
including monogamous and promiscuous voles. By
analogy with findings in those species, we speculate that
the abundance of CRF1 binding in the nucleus accumbens
of Cape mole-rats reflects their lack of affiliative behavior.http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1096-98612016-11-30am201
Unsupervised lineage-based characterization of primate precursors reveals high proliferative and morphological diversity in the OSVZ

Generation of the primate cortex is characterized by the diversity of cortical precursors and the complexity of their lineage relationships. Recent studies have reported miscellaneous precursor types based on observer classification of cell biology features including morphology, stemness, and proliferative behavior. Here we use an unsupervised machine learning method for Hidden Markov Trees (HMTs), which can be applied to large datasets to classify precursors on the basis of morphology, cell-cycle length, and behavior during mitosis. The unbiased lineage analysis automatically identifies cell types by applying a lineage-based clustering and model-learning algorithm to a macaque corticogenesis dataset. The algorithmic results validate previously reported observer classification of precursor types and show numerous advantages: It predicts a higher diversity of progenitors and numerous potential transitions between precursor types. The HMT model can be initialized to learn a user-defined number of distinct classes of precursors. This makes it possible to 1) reveal as yet undetected precursor types in view of exploring the significant features of precursors with respect to specific cellular processes; and 2) explore specific lineage features. For example, most precursors in the experimental dataset exhibit bidirectional transitions. Constraining the directionality in the HMT model leads to a reduction in precursor diversity following multiple divisions, thereby suggesting that one impact of bidirectionality in corticogenesis is to maintain precursor diversity. In this way we show that unsupervised lineage analysis provides a valuable methodology for investigating fundamental features of corticogenesis