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  • 1
    Online-Ressource
    Online-Ressource
    Large Projection Neurons in Lamina I of the Rat Spinal Cord That Lack the Neurokinin 1 Receptor Are Densely Innervated by VGLUT2-Containing Axons and Possess GluR4-Containing AMPA Receptors
    Society for Neuroscience ; 2008
    In:  The Journal of Neuroscience Vol. 28, No. 49 ( 2008-12-03), p. 13150-13160
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 28, No. 49 ( 2008-12-03), p. 13150-13160
    Kurzfassung: Although most projection neurons in lamina I express the neurokinin 1 receptor (NK1r), we have identified a population of large multipolar projection cells that lack the NK1r, are characterized by the high density of gephyrin puncta that coat their cell bodies and dendrites, and express the transcription factor Fos in response to noxious chemical stimulation. Here we show that these cells have a very high density of glutamatergic input from axons with strong immunoreactivity for vesicular glutamate transporter 2 that are likely to originate from excitatory interneurons. However, they receive few contacts from peptidergic primary afferents or transganglionically labeled Aδ nociceptors. Unlike most glutamatergic synapses in superficial laminas, those on the gephyrin-coated cells contain the GluR4 subunit of the AMPA receptor. A noxious heat stimulus caused Fos expression in 38% of the gephyrin-coated cells but in 85% of multipolar NK1r-immunoreactive cells. These findings are consistent with the suggestion that there is a correlation between function and morphology for lamina I neurons but indicate that there are at least two populations of multipolar neurons that differ in receptor expression, excitatory inputs, and responses to noxious stimulation. Although there are only ∼10 gephyrin-coated cells on each side per segment in the lumbar enlargement, they constitute ∼18% of the lamina I component of the spinothalamic tract at this level, which suggests that they play an important role in transmission of nociceptive information to the cerebral cortex. Our results also provide the first evidence that postsynaptic GluR4-containing AMPA receptors are involved in spinal nociceptive transmission.
    Materialart: Online-Ressource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.4053-08.2008
    Sprache: Englisch
    Verlag: Society for Neuroscience
    Publikationsdatum: 2008
    ZDB Id: 1475274-8
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    Inhibitory Interneurons That Express GFP in the PrP-GFP Mouse Spinal Cord Are Morphologically Heterogeneous, Innervated by Several Classes of Primary Afferent and Include Lamina I Projection Neurons among Their Postsynaptic Targets
    Society for Neuroscience ; 2015
    In:  The Journal of Neuroscience Vol. 35, No. 19 ( 2015-05-13), p. 7626-7642
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 35, No. 19 ( 2015-05-13), p. 7626-7642
    Kurzfassung: The superficial dorsal horn of the spinal cord contains numerous inhibitory interneurons, which regulate the transmission of information perceived as touch, pain, or itch. Despite the importance of these cells, our understanding of their roles in the neuronal circuitry is limited by the difficulty in identifying functional populations. One group that has been identified and characterized consists of cells in the mouse that express green fluorescent protein (GFP) under control of the prion protein (PrP) promoter. Previous reports suggested that PrP-GFP cells belonged to a single morphological class (central cells), received inputs exclusively from unmyelinated primary afferents, and had axons that remained in lamina II. However, we recently reported that the PrP-GFP cells expressed neuronal nitric oxide synthase (nNOS) and/or galanin, and it has been shown that nNOS-expressing cells are more diverse in their morphology and synaptic connections. We therefore used a combined electrophysiological, pharmacological, and anatomical approach to reexamine the PrP-GFP cells. We provide evidence that they are morphologically diverse (corresponding to “unclassified” cells) and receive synaptic input from a variety of primary afferents, with convergence onto individual cells. We also show that their axons project into adjacent laminae and that they target putative projection neurons in lamina I. This indicates that the neuronal circuitry involving PrP-GFP cells is more complex than previously recognized, and suggests that they are likely to have several distinct roles in regulating the flow of somatosensory information through the dorsal horn.
    Materialart: Online-Ressource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.0406-15.2015
    Sprache: Englisch
    Verlag: Society for Neuroscience
    Publikationsdatum: 2015
    ZDB Id: 1475274-8
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Online-Ressource
    Online-Ressource
    Evidence against AMPA Receptor-Lacking Glutamatergic Synapses in the Superficial Dorsal Horn of the Rat Spinal Cord
    Society for Neuroscience ; 2009
    In:  The Journal of Neuroscience Vol. 29, No. 42 ( 2009-10-21), p. 13401-13409
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 29, No. 42 ( 2009-10-21), p. 13401-13409
    Kurzfassung: Pure NMDA receptor (NMDAr)-mediated EPSCs, thought to correspond to “silent” glutamatergic synapses that lack AMPA receptors (AMPArs), have been observed in superficial spinal dorsal horn of neonatal but not adult rats. Recent anatomical studies suggest that AMPArs are present at virtually all glutamatergic synapses in this region in adults. We used antigen retrieval to examine colocalization of AMPArs and PSD-95 (a marker for glutamatergic synapses) in laminae I–II of neonatal and adult rats. We found a high degree of colocalization in all cases, which suggests that AMPArs are present in the great majority of glutamatergic synapses even in neonatal animals. We therefore reexamined evidence for silent synapses by performing blind whole-cell recordings from superficial dorsal horn neurons in slices from neonatal or adult rats, with focal stimulation to activate glutamatergic synapses. On some occasions in both neonatal (10 of 109, 9%) and adult (9 of 77, 12%) slices, NMDAr-mediated EPSCs were observed when the holding potential was raised to +50 mV at a stimulus strength that had failed to evoke AMPAr-mediated EPSCs. However, in all cases tested, AMPAr-mediated EPSCs were then observed when the cell was returned to −70 mV; this and other properties of the EPSCs suggest that they do not represent genuine silent synapses. When compared with previous findings, our results indicate that the appearance of silent synapses depends on experimental protocol. This suggests that pure NMDAr-mediated EPSCs seen in previous studies do not correspond to AMPAr-lacking synapses but result from another mechanism, for example, loss of labile AMPArs from recently formed synapses.
    Materialart: Online-Ressource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.2628-09.2009
    Sprache: Englisch
    Verlag: Society for Neuroscience
    Publikationsdatum: 2009
    ZDB Id: 1475274-8
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 4
    Online-Ressource
    Online-Ressource
    Projection Neurons in Lamina III of the Rat Spinal Cord Are Selectively Innervated by Local Dynorphin-Containing Excitatory Neurons
    Society for Neuroscience ; 2012
    In:  The Journal of Neuroscience Vol. 32, No. 34 ( 2012-08-22), p. 11854-11863
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 32, No. 34 ( 2012-08-22), p. 11854-11863
    Kurzfassung: Large projection neurons in lamina III of the rat spinal cord that express the neurokinin 1 receptor are densely innervated by peptidergic primary afferent nociceptors and more sparsely by low-threshold myelinated afferents. However, we know little about their input from other glutamatergic neurons. Here we show that these cells receive numerous contacts from nonprimary boutons that express the vesicular glutamate transporter 2 (VGLUT2), and form asymmetrical synapses on their dendrites and cell bodies. These synapses are significantly smaller than those formed by peptidergic afferents, but provide a substantial proportion of the glutamatergic synapses that the cells receive (over a third of those in laminae I–II and half of those in deeper laminae). Surprisingly, although the dynorphin precursor preprodynorphin (PPD) was only present in 4–7% of VGLUT2 boutons in laminae I–IV, it was found in 58% of the VGLUT2 boutons that contacted these cells. This indicates a highly selective targeting of the lamina III projection cells by glutamatergic neurons that express PPD, and these are likely to correspond to local neurons (interneurons and possibly projection cells). Since many PPD-expressing dorsal horn neurons respond to noxious stimulation, this suggests that the lamina III projection cells receive powerful monosynaptic and polysynaptic nociceptive input. Excitatory interneurons in the dorsal horn have been shown to possess I A currents, which limit their excitability and can underlie a form of activity-dependent intrinsic plasticity. It is therefore likely that polysynaptic inputs to the lamina III projection neurons are recruited during the development of chronic pain states.
    Materialart: Online-Ressource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.2707-12.2012
    Sprache: Englisch
    Verlag: Society for Neuroscience
    Publikationsdatum: 2012
    ZDB Id: 1475274-8
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
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