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Neurons in the lateral part of the lumbar spinal cord show distinct novel axon trajectories and are excited by short propriospinal ascending inputs

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An Erratum to this article was published on 19 May 2015

Abstract

The role of spinal dorsal horn propriospinal connections in nociceptive processing is not yet established. Recently described, rostrocaudally oriented axon collaterals of lamina I projection and local-circuit neurons (PNs and LCNs) running in the dorsolateral funiculus (DLF) may serve as the anatomical substrate for intersegmental processing. Putative targets of these axons include lateral dendrites of superficial dorsal horn neurons, including PNs, and also neurons in the lateral spinal nucleus (LSN) that are thought to be important integrator units receiving, among others, visceral sensory information. Here we used an intact spinal cord preparation to study intersegmental connections within the lateral part of the superficial dorsal horn. We detected brief monosynaptic and prolonged polysynaptic excitation of lamina I and LSN neurons when stimulating individual dorsal horn neurons located caudally, even in neighboring spinal cord segments. These connections, however, were infrequent. We also revealed that some projection neurons outside the dorsal grey matter and in the LSN have distinct, previously undescribed course of their projection axon. Our findings indicate that axon collaterals of lamina I PNs and LCNs in the DLF rarely form functional connections with other lamina I and LSN neurons and that the majority of their targets are on other elements of the dorsal horn. The unique axon trajectories of neurons in the dorsolateral aspect of the spinal cord, including the LSN do not fit our present understanding of midline axon guidance and suggest that their function and development differ from the neurons inside lamina I. These findings emphasize the importance of understanding the connectivity matrix of the superficial dorsal horn in order to decipher spinal sensory information processing.

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References

  • Aguiar P, Sousa M, Szucs P (2013) Versatile morphometric analysis and visualization of the three-dimensional structure of neurons. Neuroinformatics 11(4):393–403

    Article  PubMed  Google Scholar 

  • Al-Khater KM, Todd AJ (2009) Collateral projections of neurons in laminae I, III, and IV of rat spinal cord to thalamus, periaqueductal gray matter, and lateral parabrachial area. J Comp Neurol 515(6):629–646

    Article  PubMed  PubMed Central  Google Scholar 

  • Augsburger A, Schuchardt A, Hoskins S, Dodd J, Butler S (1999) BMPs as mediators of roof plate repulsion of commissural neurons. Neuron 24(1):127–141

    Article  CAS  PubMed  Google Scholar 

  • Braz J, Solorzano C, Wang X, Basbaum AI (2014) Transmitting pain and itch messages: a contemporary view of the spinal cord circuits that generate gate control. Neuron 82(3):522–536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bresnahan JC, Ho RH, Beattie MS (1984) A comparison of the ultrastructure of substance P and enkephalin-immunoreactive elements in the nucleus of the dorsal lateral funiculus and laminae I and II of the rat spinal cord. J Comp Neurol 229(4):497–511

    Article  CAS  PubMed  Google Scholar 

  • Burstein R, Giesler GJ Jr (1989) Retrograde labeling of neurons in spinal cord that project directly to nucleus accumbens or the septal nuclei in the rat. Brain Res 497(1):149–154

    Article  CAS  PubMed  Google Scholar 

  • Burstein R, Potrebic S (1993) Retrograde labeling of neurons in the spinal cord that project directly to the amygdala or the orbital cortex in the rat. J Comp Neurol 335(4):469–485

    Article  CAS  PubMed  Google Scholar 

  • Burstein R, Cliffer KD, Giesler GJ Jr (1990) Cells of origin of the spinohypothalamic tract in the rat. J Comp Neurol 291(3):329–344

    Article  CAS  PubMed  Google Scholar 

  • Charron F, Stein E, Jeong J, McMahon AP, Tessier-Lavigne M (2003) The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell 113(1):11–23

    Article  CAS  PubMed  Google Scholar 

  • Chen Z, Gore BB, Long H, Ma L, Tessier-Lavigne M (2008) Alternative splicing of the Robo3 axon guidance receptor governs the midline switch from attraction to repulsion. Neuron 58(3):325–332

    Article  CAS  PubMed  Google Scholar 

  • Cliffer KD, Urca G, Elde RP, Giesler GJ Jr (1988) Studies of peptidergic input to the lateral spinal nucleus. Brain Res 460(2):356–360

    Article  CAS  PubMed  Google Scholar 

  • Ding YQ, Takada M, Shigemoto R, Mizumo N (1995) Spinoparabrachial tract neurons showing substance P receptor-like immunoreactivity in the lumbar spinal cord of the rat. Brain Res 674(2):336–340

    Article  CAS  PubMed  Google Scholar 

  • Dutton RC, Carstens MI, Antognini JF, Carstens E (2006) Long ascending propriospinal projections from lumbosacral to upper cervical spinal cord in the rat. Brain Res 1119(1):76–85

    Article  CAS  PubMed  Google Scholar 

  • Escalante A, Murillo B, Morenilla-Palao C, Klar A, Herrera E (2013) Zic2-dependent axon midline avoidance controls the formation of major ipsilateral tracts in the CNS. Neuron 80(6):1392–1406

    Article  CAS  PubMed  Google Scholar 

  • Esteves F, Lima D, Coimbra A (1993) Structural types of spinal cord marginal (lamina I) neurons projecting to the nucleus of the tractus solitarius in the rat. Somatosens Mot Res 10(2):203–216

    Article  CAS  PubMed  Google Scholar 

  • Etlin A, Blivis D, Ben-Zwi M, Lev-Tov A (2010) Long and short multifunicular projections of sacral neurons are activated by sensory input to produce locomotor activity in the absence of supraspinal control. J Neurosci 30(31):10324–10336

    Article  CAS  PubMed  Google Scholar 

  • Feil K, Herbert H (1995) Topographic organization of spinal and trigeminal somatosensory pathways to the rat parabrachial and Kolliker-Fuse nuclei. J Comp Neurol 353(4):506–528

    Article  CAS  PubMed  Google Scholar 

  • Gauriau C, Bernard JF (2004) A comparative reappraisal of projections from the superficial laminae of the dorsal horn in the rat: the forebrain. J Comp Neurol 468(1):24–56

    Article  PubMed  Google Scholar 

  • Giesler GJ Jr, Elde RP (1985) Immunocytochemical studies of the peptidergic content of fibers and terminals within the lateral spinal and lateral cervical nuclei. J Neurosci 5(7):1833–1841

    CAS  PubMed  Google Scholar 

  • Gwyn DG, Waldron HA (1968) A nucleus in the dorsolateral funiculus of the spinal cord of the rat. Brain Res 10(3):342–351

    Article  CAS  PubMed  Google Scholar 

  • Gwyn DG, Waldron HA (1969) Observations on the morphology of a nucleus in the dorsolateral funiculus of the spinal cord of the guinea-pig, rabbit, ferret and cat. J Comp Neurol 136(2):233–236

    Article  CAS  PubMed  Google Scholar 

  • Harmann PA, Carlton SM, Willis WD (1988) Collaterals of spinothalamic tract cells to the periaqueductal gray: a fluorescent double-labeling study in the rat. Brain Res 441(1–2):87–97

    Article  CAS  PubMed  Google Scholar 

  • Jansen AS, Loewy AD (1997) Neurons lying in the white matter of the upper cervical spinal cord project to the intermediolateral cell column. Neuroscience 77(3):889–898

    Article  CAS  PubMed  Google Scholar 

  • Juvin L, Simmers J, Morin D (2005) Propriospinal circuitry underlying interlimb coordination in mammalian quadrupedal locomotion. J Neurosci 25(25):6025–6035

    Article  CAS  PubMed  Google Scholar 

  • Kato G, Kawasaki Y, Koga K, Uta D, Kosugi M, Yasaka T, Yoshimura M, Ji RR, Strassman AM (2009) Organization of intralaminar and translaminar neuronal connectivity in the superficial spinal dorsal horn. J Neurosci 29(16):5088–5099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kennedy TE, Serafini T, de la Torre JR, Tessier-Lavigne M (1994) Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord. Cell 78(3):425–435

    Article  CAS  PubMed  Google Scholar 

  • Leah J, Menetrey D, de Pommery J (1988) neuropeptides in long ascending spinal tract cells in the rat: evidence for parallel processing of ascending information. Neuroscience 24(1):195–207

    Article  CAS  PubMed  Google Scholar 

  • Lee DC, Jensen AL, Schiefer MA, Morgan CW, Grill WM (2005) Structural mechanisms to produce differential dendritic gains. Brain Res 1033(2):117–127

    Article  CAS  PubMed  Google Scholar 

  • Lima D (1998) Anatomical basis for the dynamic processing of nociceptive input. Eur J Pain 2(3):195–202

    Article  CAS  PubMed  Google Scholar 

  • Lima D, Coimbra A (1986) A Golgi study of the neuronal population of the marginal zone (lamina I) of the rat spinal cord. J Comp Neurol 244(1):53–71

    Article  CAS  PubMed  Google Scholar 

  • Long H, Sabatier C, Ma L, Plump A, Yuan W, Ornitz DM, Tamada A, Murakami F, Goodman CS, Tessier-Lavigne M (2004) Conserved roles for Slit and Robo proteins in midline commissural axon guidance. Neuron 42(2):213–223

    Article  CAS  PubMed  Google Scholar 

  • Lu Y, Perl ER (2003) A specific inhibitory pathway between substantia gelatinosa neurons receiving direct C-fiber input. J Neurosci 23(25):8752–8758

    CAS  PubMed  Google Scholar 

  • Lu Y, Perl ER (2005) Modular organization of excitatory circuits between neurons of the spinal superficial dorsal horn (laminae I and II). J Neurosci 25(15):3900–3907

    Article  CAS  PubMed  Google Scholar 

  • Luz LL, Szucs P, Pinho R, Safronov BV (2010) Monosynaptic excitatory inputs to spinal lamina I anterolateral-tract-projecting neurons from neighbouring lamina I neurons. J Physiol 588(22):4489–4505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Menetrey D, Basbaum AI (1987) Spinal and trigeminal projections to the nucleus of the solitary tract: a possible substrate for somatovisceral and viscerovisceral reflex activation. J Comp Neurol 255(3):439–450

    Article  CAS  PubMed  Google Scholar 

  • Menetrey D, Chaouch A, Binder D, Besson JM (1982) The origin of the spinomesencephalic tract in the rat: an anatomical study using the retrograde transport of horseradish peroxidase. J Comp Neurol 206(2):193–207

    Article  CAS  PubMed  Google Scholar 

  • Olave MJ, Maxwell DJ (2004) Axon terminals possessing alpha2C-adrenergic receptors densely innervate neurons in the rat lateral spinal nucleus which respond to noxious stimulation. Neuroscience 126(2):391–403

    Article  CAS  PubMed  Google Scholar 

  • Pechura CM, Liu RP (1986) Spinal neurons which project to the periaqueductal gray and the medullary reticular formation via axon collaterals: a double-label fluorescence study in the rat. Brain Res 374(2):357–361

    Article  CAS  PubMed  Google Scholar 

  • Petko M, Antal M (2000) Propriospinal afferent and efferent connections of the lateral and medial areas of the dorsal horn (laminae I-IV) in the rat lumbar spinal cord. J Comp Neurol 422(2):312–325

    Article  CAS  PubMed  Google Scholar 

  • Petko M, Veress G, Vereb G, Storm-Mathisen J, Antal M (2004) Commissural propriospinal connections between the lateral aspects of laminae III-IV in the lumbar spinal cord of rats. J Comp Neurol 480(4):364–377

    Article  PubMed  Google Scholar 

  • Pinto V, Szucs P, Lima D, Safronov BV (2010) Multisegmental Aδ-and C-fiber input to neurons in lamina I and the lateral spinal nucleus. J Neurosci 30(6):2384–2395

    Article  CAS  PubMed  Google Scholar 

  • Reed WR, Shum-siu A, Onifer SM, Magnuson DSK (2006) Inter-enlargement pathways in the ventrolateral funiculus of the adult rat spinal cord. Neuroscience 142:1195–1207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rethelyi M (2003) Neurons of the lateral spinal nucleus in the rat spinal cord—a Golgi study. Eur J Anat 7(1):8

    Google Scholar 

  • Sabatier C, Plump AS, Le M, Brose K, Tamada A, Murakami F, Lee EY, Tessier-Lavigne M (2004) The divergent Robo family protein rig-1/Robo3 is a negative regulator of slit responsiveness required for midline crossing by commissural axons. Cell 117(2):157–169

    Article  CAS  PubMed  Google Scholar 

  • Safronov BV, Pinto V, Derkach VA (2007) High-resolution single-cell imaging for functional studies in the whole brain and spinal cord and thick tissue blocks using light-emitting diode illumination. J Neurosci Methods 164(2):292–298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santos SF, Rebelo S, Derkach VA, Safronov BV (2007) Excitatory interneurons dominate sensory processing in the spinal substantia gelatinosa of rat. J Physiol 581(Pt 1):241–254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santos SF, Luz LL, Szucs P, Lima D, Derkach VA, Safronov BV (2009) Transmission efficacy and plasticity in glutamatergic synapses formed by excitatory interneurons of the substantia gelatinosa in the rat spinal cord. PLoS One 4(11):e8047

    Article  PubMed  PubMed Central  Google Scholar 

  • Seybold V, Elde R (1980) Immunohistochemical studies of peptidergic neurons in the dorsal horn of the spinal cord. J Histochem Cytochem 28(4):367–370

    Article  CAS  PubMed  Google Scholar 

  • Sugiura Y, Terui N, Hosoya Y (1989) Difference in distribution of central terminals between visceral and somatic unmyelinated (C) primary afferent fibers. J Neurophysiol 62(4):834–840

    CAS  PubMed  Google Scholar 

  • Szentagothai J (1964) Neuronal and synaptic arrangement in the substantia gelatinosa Rolandi. J Comp Neurol 122:219–239

    Article  CAS  PubMed  Google Scholar 

  • Szucs P, Pinto V, Safronov BV (2009) Advanced technique of infrared LED imaging of unstained cells and intracellular structures in isolated spinal cord, brainstem, ganglia and cerebellum. J Neurosci Methods 177(2):369–380

    Article  CAS  PubMed  Google Scholar 

  • Szucs P, Luz LL, Lima D, Safronov BV (2010) Local axon collaterals of lamina I projection neurons in the spinal cord of young rats. J Comp Neurol 518(14):2645–2665

    Article  PubMed  Google Scholar 

  • Szucs P, Luz LL, Pinho R, Aguiar P, Antal Z, Tiong SY, Todd AJ, Safronov BV (2013) Axon diversity of lamina I local-circuit neurons in the lumbar spinal cord. J Comp Neurol 521(12):2719–2741

    Article  PubMed  PubMed Central  Google Scholar 

  • Thome C, Kelly T, Yanez A, Schultz C, Engelhardt M, Cambridge SB, Both M, Draguhn A, Beck H, Egorov AV (2014) Axon-carrying dendrites convey privileged synaptic input in hippocampal neurons. Neuron 83(6):1418–1430

    Article  CAS  PubMed  Google Scholar 

  • Todd AJ (2010) Neuronal circuitry for pain processing in the dorsal horn. Nat Rev Neurosci 11(12):823–836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verburgh CA, Voogd J, Kuypers HG, Stevens HP (1990) Propriospinal neurons with ascending collaterals to the dorsal medulla, the thalamus and the tectum: a retrograde fluorescent double-labeling study of the cervical cord of the rat. Exp Brain Res 80(3):577–590

    Article  CAS  PubMed  Google Scholar 

  • Zou Y, Stoeckli E, Chen H, Tessier-Lavigne M (2000) Squeezing axons out of the gray matter: a role for slit and semaphorin proteins from midline and ventral spinal cord. Cell 102(3):363–375

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by FEDER funds through the Operational Competitiveness Programme—COMPETE and by national funds through FCT—Fundação para a Ciência e a Tecnologia under the project FCOMP-01-0124-FEDER-029632 (PTDC/NEU-SCC/0347/2012 to BS), the Hungarian Academy of Sciences (MTA-TKI 242 to MA), the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (PSz), the Hungarian Brain Research Program (KTIA_NAP_ 13-2-2014-0005 to PSz and KTIA_NAP_13-1-2013-0001 to MA) and TÁMOP-4.2.4.A/2-11/1-2012-0001 ‘National Excellence Program’ supported by the Sate of Hungary and the European Union, co-financed by the European Social Fund (ZsA). The authors are grateful to Raquel Pinho for her excellent help with the histological processing and reconstruction.

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Authors and Affiliations

  1. Department of Anatomy, Histology and Embryology, Univerity of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary

    Zs. Antal & M. Antal

  2. Neuronal Networks Group, Instituto de Biologia Molecular e Celular-IBMC, Universidade do Porto, Rua do Campo Alegre 823, 4150-180, Porto, Portugal

    L. L. Luz, B. V. Safronov & Peter Szücs

  3. MTA-DE Neuroscience Research Group, Debrecen, 4012, Hungary

    M. Antal

  4. MTA-DE-NAP B-Pain Control Research Group, Nagyerdei krt. 98, Debrecen, 4032, Hungary

    Peter Szücs

  5. Department of Physiology, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary

    Peter Szücs

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  1. Zs. Antal
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Correspondence to Peter Szücs.

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Antal, Z., Luz, L.L., Safronov, B.V. et al. Neurons in the lateral part of the lumbar spinal cord show distinct novel axon trajectories and are excited by short propriospinal ascending inputs. Brain Struct Funct 221, 2343–2360 (2016). https://doi.org/10.1007/s00429-015-1046-3

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