Advertisement

Biogerontology

, Volume 19, Issue 5, pp 385–399 | Cite as

Age-related loss of VGLUT1 excitatory, but not VGAT inhibitory, immunoreactive terminals on motor neurons in spinal cords of old sarcopenic male mice

  • Vidya S. Krishnan
  • Tea Shavlakadze
  • Miranda D. Grounds
  • Stuart I. Hodgetts
  • Alan R. Harvey
Research Article

Abstract

Age-related changes in ventral lumbar spinal cord (L3–L5) were compared in young [3 month, (M)] and old (27 M) C57BL/6J male mice. The aged mice had previously been shown to exhibit sarcopenia and changes to peripheral nerve morphology. The putative connectivity of β-III tubulin positive α-motor neurons was compared in immunostained transverse sections using excitatory and inhibitory terminal markers vesicular glutamate transporter-1 (VGLUT1) and vesicular GABA transporter (VGAT). Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) immunostaining was used to monitor changes in astrocyte and microglial phenotype respectively. For a given motor neuron, the neuronal perimeter was outlined and terminals immunoreactive for VGLUT1 or VGAT in close apposition to the soma were identified. By 27 M, the percentage coverage and total number of VGLUT1 immunoreactive terminals immediately adjacent to the soma of α-motor neurons was significantly decreased compared with young mice. However, percentage coverage of immunoreactive VGAT inhibitory terminals did not change significantly with age. The gray matter of 27 M spinal cords showed increased astrocytic and microglial activity. The loss of VGLUT1 terminals on α-motor neurons, terminals known to be derived from proprioceptive muscle afferents, may further impair sensorimotor control of hind limb skeletal muscle function in old mice.

Keywords

VGLUT1 VGAT Astrocytes Microglia Synaptic transmission Proprioception Sarcopenia 

Notes

Acknowledgements

This research was made possible by funding from a Central grant from the University of Western Australia (UWA, for MG), the WA Neurotrauma Research Programme (for MG, ARH, SH and VSK), and an International Postgraduate Scholarship and a Postgraduate Scholarship for International Tuition Fees from UWA (for VSK). We thank Professor Charles Watson for helpful discussions.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

References

  1. Aagaard P, Suetta C, Caserotti P, Magnusson SP, Kjaer M (2010) Role of the nervous system in sarcopenia and muscle atrophy with aging: strength training as a countermeasure. Scand J Med Sci Sports 20:49–64CrossRefPubMedGoogle Scholar
  2. Akay T, Tourtellotte WG, Arber S, Jessell TM (2014) Degradation of mouse locomotor pattern in the absence of proprioceptive sensory feedback. Proc Natl Acad Sci 111:16877–16882CrossRefPubMedGoogle Scholar
  3. Alvarez FJ, Villalba RM, Zerda R, Schneider SP (2004) Vesicular glutamate transporters in the spinal cord, with special reference to sensory primary afferent synapses. J Comp Neurol 472:257–280CrossRefPubMedGoogle Scholar
  4. Alvarez FJ, Titus-Mitchell HE, Bullinger KL, Kraszpulski M, Nardelli P, Cope TC (2011) Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. I. Loss of VGLUT1/IA synapses on motoneurons. J Neurophysiol 106:2450–2470CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bala U, Tan KL, Ling KH, Cheah PS (2014) Harvesting the maximum length of sciatic nerve from adult mice: a step-by-step approach. BMC Res Notes 7:714CrossRefPubMedPubMedCentralGoogle Scholar
  6. Balschun D, Moechars D, Callaerts-Vegh Z, Vermaercke B, Van Acker N, Andries L, D’Hooge R (2010) Vesicular glutamate transporter VGLUT1 has a role in hippocampal long-term potentiation and spatial reversal learning. Cereb Cortex 20:684–693CrossRefPubMedGoogle Scholar
  7. Banuelos C, Beas BS, McQuail JA, Gilbert RJ, Frazier CJ, Setlow B, Bizon JL (2014) Prefrontal cortical GABAergic dysfunction contributes to age-related working memory impairment. J Neurosci 34:3457–3466CrossRefPubMedPubMedCentralGoogle Scholar
  8. Barbeito LH et al (2004) A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis. Brain Res Brain Res Rev 47:263–274CrossRefPubMedGoogle Scholar
  9. Barrett CP, Guth L, Donati EJ, Krikorian JG (1981) Astroglial reaction in the gray matter lumbar segments after midthoracic transection of the adult rat spinal cord. Exp Neurol 73:365–377CrossRefPubMedGoogle Scholar
  10. Bernardinelli Y, Muller D, Nikonenko I (2014) Astrocyte-synapse structural plasticity. Neural Plast 2014:232105CrossRefPubMedPubMedCentralGoogle Scholar
  11. Brettschneider J, Toledo JB, Van Deerlin VM, Elman L, McCluskey L, Lee VM, Trojanowski JQ (2012) Microglial activation correlates with disease progression and upper motor neuron clinical symptoms in amyotrophic lateral sclerosis. PLoS ONE 7:e39216CrossRefPubMedPubMedCentralGoogle Scholar
  12. Brumovsky PR (2013) VGLUTs in peripheral neurons and the spinal cord: time for a review. ISRN Neurol 2013:829753CrossRefPubMedPubMedCentralGoogle Scholar
  13. Brumovsky P, Watanabe M, Hokfelt T (2007) Expression of the vesicular glutamate transporters-1 and -2 in adult mouse dorsal root ganglia and spinal cord and their regulation by nerve injury. Neuroscience 147:469–490CrossRefPubMedGoogle Scholar
  14. Canas PM, Duarte JM, Rodrigues RJ, Kofalvi A, Cunha RA (2009) Modification upon aging of the density of presynaptic modulation systems in the hippocampus. Neurobiol Aging 30:1877–1884CrossRefPubMedGoogle Scholar
  15. Casale EJ, Light AR, Rustioni A (1988) Direct projection of the corticospinal tract to the superficial laminae of the spinal cord in the rat. J Comp Neurol 278:275–286CrossRefPubMedGoogle Scholar
  16. Chai RJ, Vukovic J, Dunlop S, Grounds MD, Shavlakadze T (2011) Striking denervation of neuromuscular junctions without lumbar motoneuron loss in geriatric mouse muscle. PLoS ONE 6:1–11Google Scholar
  17. Clark AK, Gruber-Schoffnegger D, Drdla-Schutting R, Gerhold KJ, Malcangio M, Sandkuhler J (2015) Selective activation of microglia facilitates synaptic strength. J Neurosci 35:4552–4570CrossRefPubMedPubMedCentralGoogle Scholar
  18. D’Acunzo P, Badaloni A, Ferro M, Ripamonti M, Zimarino V, Malgaroli A, Consalez GG (2014) A conditional transgenic reporter of presynaptic terminals reveals novel features of the mouse corticospinal tract. Front Neuroanat 7:50PubMedPubMedCentralCrossRefGoogle Scholar
  19. Damoiseaux JG, Dopp EA, Calame W, Chao D, MacPherson GG, Dijkstra CD (1994) Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. Immunology 83:140–147PubMedPubMedCentralGoogle Scholar
  20. Deak F, Sonntag WE (2012) Aging, synaptic dysfunction, and insulin-like growth factor (IGF)-1. J Gerontol 67:611–625CrossRefGoogle Scholar
  21. Doherty TJ (2003) Invited review: aging and sarcopenia. J Appl Physiol 95:1717–1727CrossRefPubMedGoogle Scholar
  22. Drey M, Krieger B, Sieber CC, Bauer JM, Hettwer S, Bertsch T, DISARCO Study Group (2014) Motoneuron loss is associated with sarcopenia. J Am Med Dir Assoc 15:435–439CrossRefPubMedGoogle Scholar
  23. Duan W, Zhang R, Guo Y, Jiang Y, Huang Y, Jiang H, Li C (2009) Nrf2 activity is lost in the spinal cord and its astrocytes of aged mice. In Vitro Cell Dev Biol Anim 45:388–397CrossRefPubMedGoogle Scholar
  24. Edstrom E, Altun M, Bergman E, Johnson H, Kullberg S, Ramirez-Leon V, Ulfhake B (2007) Factors contributing to neuromuscular impairment and sarcopenia during aging. Physiol Behav 92:129–135CrossRefPubMedGoogle Scholar
  25. Fremeau RT Jr et al (2004) Vesicular glutamate transporters 1 and 2 target to functionally distinct synaptic release sites. Science 304:1815–1819CrossRefPubMedGoogle Scholar
  26. Friese A, Kaltschmidt JA, Ladle DR, Sigrist M, Jessell TM, Arber S (2009) Gamma and alpha motor neurons distinguished by expression of transcription factor Err3. Proc Natl Acad Sci 106:13588–13593CrossRefPubMedGoogle Scholar
  27. Hashizume K, Kanda K (1995) Differential effects of aging on motoneurons and peripheral nerves innervating the hindlimb and forelimb muscles of rats. Neurosci Res 22:189–196CrossRefPubMedGoogle Scholar
  28. Hodgetts SI, Simmons PJ, Plant GW (2013) A comparison of the behavioral and anatomical outcomes in sub-acute and chronic spinal cord injury models following treatment with human mesenchymal precursor cell transplantation and recombinant decorin. Exp Neurol 248:343–359CrossRefPubMedGoogle Scholar
  29. Hu D, Serrano F, Oury TD, Klann E (2006) Aging-dependent alterations in synaptic plasticity and memory in mice that overexpress extracellular superoxide dismutase. J Neurosci 26:3933–3941CrossRefPubMedGoogle Scholar
  30. Jacob JM (1998) Lumbar motor neuron size and number is affected by age in male F344 rats. Mech Ageing Dev 106:205–216CrossRefPubMedGoogle Scholar
  31. Jouhilahti EM, Peltonen S, Peltonen J (2008) Class III beta-tubulin is a component of the mitotic spindle in multiple cell types. J Histochem Cytochem 56:1113–1119CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kane CJ, Sims TJ, Gilmore SA (1997) Astrocytes in the aged rat spinal cord fail to increase GFAP mRNA following sciatic nerve axotomy. Brain Res 759:163–165CrossRefPubMedGoogle Scholar
  33. Kanning KC, Kaplan A, Henderson CE (2010) Motor neuron diversity in development and disease. Annu Rev Neurosci 33:409–440CrossRefPubMedGoogle Scholar
  34. Karimi-Abdolrezaee S, Billakanti R (2012) Reactive astrogliosis after spinal cord injury-beneficial and detrimental effects. Mol Neurobiol 46:251–264CrossRefPubMedGoogle Scholar
  35. Kawamura Y, O’Brien P, Okazaki H, Dyck PJ (1977) Lumbar motoneurons of man II: the number and diameter distribution of large- and intermediate-diameter cytons in “motoneuron columns” of spinal cord of man. J Neuropathol Exp Neurol 36:861–870CrossRefPubMedGoogle Scholar
  36. Kirkpatrick LJ, Yablonka-Reuveni Z, Rosser BW (2010) Retention of Pax3 expression in satellite cells of muscle spindles. J Histochem Cytochem 58:317–327CrossRefPubMedPubMedCentralGoogle Scholar
  37. Krishnan VS et al (2016) A neurogenic perspective of sarcopenia: time course study of sciatic nerves from aging mice. J Neuropathol Exp Neurol 75:464–478CrossRefPubMedGoogle Scholar
  38. Kullberg S, Ramirez-Leon V, Johnson H, Ulfhake B (1998) Decreased axosomatic input to motoneurons and astrogliosis in the spinal cord of aged rats. J Gerontol 53:B369–B379CrossRefGoogle Scholar
  39. Kullberg S, Aldskogius H, Ulfhake B (2001) Microglial activation, emergence of ED1-expressing cells and clusterin upregulation in the aging rat CNS, with special reference to the spinal cord. Brain Res 899:169–186CrossRefPubMedGoogle Scholar
  40. Kwan P (2013) Sarcopenia: the gliogenic perspective. Mech Ageing Dev 134:349–355CrossRefPubMedGoogle Scholar
  41. Lee S, Wu Y, Shi XQ, Zhang J (2015) Characteristics of spinal microglia in aged and obese mice: potential contributions to impaired sensory behavior. Immun Ageing 12:22CrossRefPubMedPubMedCentralGoogle Scholar
  42. Levine AJ, Hinckley CA, Hilde KL, Driscoll SP, Poon TH, Montgomery JM, Pfaff SL (2014) Identification of a cellular node for motor control pathways. Nat Neurosci 17:586–593CrossRefPubMedPubMedCentralGoogle Scholar
  43. Lexell J (1997) Evidence for nervous system degeneration with advancing age. J Nutr 127:1011S–1013SCrossRefPubMedGoogle Scholar
  44. Li JL, Fujiyama F, Kaneko T, Mizuno N (2003) Expression of vesicular glutamate transporters, VGluT1 and VGluT2, in axon terminals of nociceptive primary afferent fibers in the superficial layers of the medullary and spinal dorsal horns of the rat. J Comp Neurol 457:236–249CrossRefPubMedGoogle Scholar
  45. Liguz-Lecznar M, Lehner M, Kaliszewska A, Zakrzewska R, Sobolewska A, Kossut M (2015) Altered glutamate/GABA equilibrium in aged mice cortex influences cortical plasticity. Brain Struct Funct 220:1681–1693CrossRefPubMedGoogle Scholar
  46. Ling KK, Lin MY, Zingg B, Feng Z, Ko CP (2010) Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy. PLoS ONE 5:e15457CrossRefPubMedPubMedCentralGoogle Scholar
  47. Liu C, Ward PJ, English AW (2014) The effects of exercise on synaptic stripping require androgen receptor signaling. PLoS ONE 9:e98633CrossRefPubMedPubMedCentralGoogle Scholar
  48. Lord SR, Ward JA (1994) Age-associated differences in sensori-motor function and balance in community dwelling women. Age Ageing 23:452–460CrossRefPubMedGoogle Scholar
  49. Lynch AM et al (2010) The impact of glial activation in the aging brain. Aging Dis 1:262–278PubMedPubMedCentralGoogle Scholar
  50. Maeda H et al (2016) Corticospinal axons make direct synaptic connections with spinal motoneurons innervating forearm muscles early during postnatal development in the rat. J Physiol 594:189–205CrossRefPubMedGoogle Scholar
  51. Martin JE et al (2017) Decreased motor neuron support by SMA astrocytes due to diminished MCP1 secretion. J Neurosci 37:5309–5318CrossRefPubMedPubMedCentralGoogle Scholar
  52. Maxwell N et al (2018) alpha-Motor neurons are spared from aging while their synaptic inputs degenerate in monkeys and mice. Aging Cell.  https://doi.org/10.1111/acel.12726 PubMedPubMedCentralCrossRefGoogle Scholar
  53. McIntire SL, Reimer RJ, Schuske K, Edwards RH, Jorgensen EM (1997) Identification and characterization of the vesicular GABA transporter. Nature 389:870–876CrossRefPubMedGoogle Scholar
  54. Mentis GZ et al (2011) Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy. Neuron 69:453–467CrossRefPubMedPubMedCentralGoogle Scholar
  55. Misawa H, Hara M, Tanabe S, Niikura M, Moriwaki Y, Okuda T (2012) Osteopontin is an alpha motor neuron marker in the mouse spinal cord. J Neurosci Res 90:732–742CrossRefPubMedGoogle Scholar
  56. Mittal KR, Logmani FH (1987) Age-related reduction in 8th cervical ventral nerve root myelinated fiber diameters and numbers in man. J Gerontol 42:8–10CrossRefPubMedGoogle Scholar
  57. Monti B, Virgili M, Contestabile A (2004) Alterations of markers related to synaptic function in aging rat brain, in normal conditions or under conditions of long-term dietary manipulation. Neurochem Int 44:579–584CrossRefPubMedGoogle Scholar
  58. Morisaki Y et al (2016) Selective expression of osteopontin in ALS-resistant motor neurons is a critical determinant of late phase neurodegeneration mediated by matrix metalloproteinase-9. Sci Rep 6:27354CrossRefPubMedPubMedCentralGoogle Scholar
  59. Nakajima K, Kohsaka S (2001) Microglia: activation and their significance in the central nervous system. J Biochem 130:169–175CrossRefPubMedGoogle Scholar
  60. Norden DM, Godbout JP (2013) Review: microglia of the aged brain: primed to be activated and resistant to regulation. Neuropathol Appl Neurobiol 39:19–34CrossRefPubMedPubMedCentralGoogle Scholar
  61. Oliveira AL et al (2003) Cellular localization of three vesicular glutamate transporter mRNAs and proteins in rat spinal cord and dorsal root ganglia. Synapse 50:117–129CrossRefPubMedGoogle Scholar
  62. Owens DF, Kriegstein AR (2002) Is there more to GABA than synaptic inhibition? Nat Rev Neurosci 3:715–727CrossRefPubMedGoogle Scholar
  63. Pannerec A et al (2016) A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia. Aging 8:712–729CrossRefPubMedPubMedCentralGoogle Scholar
  64. Persson S et al (2006) Distribution of vesicular glutamate transporters 1 and 2 in the rat spinal cord, with a note on the spinocervical tract. J Comp Neurol 497:683–701CrossRefPubMedGoogle Scholar
  65. Petralia RS, Mattson MP, Yao PJ (2014) Communication breakdown: the impact of ageing on synapse structure. Ageing Res Rev 14:31–42CrossRefPubMedPubMedCentralGoogle Scholar
  66. Proske U, Wise AK, Gregory JE (2000) The role of muscle receptors in the detection of movements. Progress Neurobiol 60:85–96CrossRefGoogle Scholar
  67. Purves D (2001) Neuroscience. The motor unit, 2nd edn. Sinauer Associates, SunderlandGoogle Scholar
  68. Ranson RN, Santer RM, Watson AH (2007) Ageing reduces the number of vesicular glutamate transporter 2 containing immunoreactive inputs to identified rat pelvic motoneurons. Exp Gerontol 42:506–516CrossRefPubMedGoogle Scholar
  69. Ribeiro F, Oliveira J (2007) Aging effects on joint proprioception: the role of physical activity in proprioception preservation. Eur Rev Aging Phys Act 4:71–76CrossRefGoogle Scholar
  70. Ridet JL, Malhotra SK, Privat A, Gage FH (1997) Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci 20:570–577CrossRefPubMedGoogle Scholar
  71. Rigaud M, Gemes G, Barabas ME, Chernoff DI, Abram SE, Stucky CL, Hogan QH (2008) Species and strain differences in rodent sciatic nerve anatomy: implications for studies of neuropathic pain. Pain 136:188–201CrossRefPubMedPubMedCentralGoogle Scholar
  72. Ritzel RM, Patel AR, Pan S, Crapser J, Hammond M, Jellison E, McCullough LD (2015) Age- and location-related changes in microglial function. Neurobiol Aging 36:2153–2163CrossRefPubMedGoogle Scholar
  73. Rodriguez-Arellano JJ, Parpura V, Zorec R, Verkhratsky A (2016) Astrocytes in physiological aging and Alzheimer’s disease. Neuroscience 323:170–182CrossRefPubMedGoogle Scholar
  74. Rotterman TM, Nardelli P, Cope TC, Alvarez FJ (2014) Normal distribution of VGLUT1 synapses on spinal motoneuron dendrites and their reorganization after nerve injury. J Neurosci 34:3475–3492CrossRefPubMedPubMedCentralGoogle Scholar
  75. Rozycka A, Liguz-Lecznar M (2017) The space where aging acts: focus on the GABAergic synapse. Aging Cell 16:634–643CrossRefPubMedPubMedCentralGoogle Scholar
  76. Sasaki Y, Ohsawa K, Kanazawa H, Kohsaka S, Imai Y (2001) Iba1 is an actin-cross-linking protein in macrophages/microglia. Biochem Biophys Res Commun 286:292–297CrossRefPubMedGoogle Scholar
  77. Schmidt S, Redecker C, Bruehl C, Witte OW (2010) Age-related decline of functional inhibition in rat cortex. Neurobiol Aging 31:504–511CrossRefPubMedGoogle Scholar
  78. Siskova Z, Tremblay ME (2013) Microglia and synapse: interactions in health and neurodegeneration. Neural Plast 2013:425845CrossRefPubMedPubMedCentralGoogle Scholar
  79. Soffe Z, Radley-Crabb HG, McMahon C, Grounds MD, Shavlakadze T (2016) Effects of loaded voluntary wheel exercise on performance and muscle hypertrophy in young and old male C57BL/6J mice. Scand J Med Sci Sports 26:172–188CrossRefPubMedGoogle Scholar
  80. Sorensen KL, Hollands MA, Patla E (2002) The effects of human ankle muscle vibration on posture and balance during adaptive locomotion. Exp Brain Res 43:24–34CrossRefGoogle Scholar
  81. Stanley EM, Fadel JR, Mott DD (2012) Interneuron loss reduces dendritic inhibition and GABA release in hippocampus of aged rats. Neurobiol Aging 33:431-e1CrossRefGoogle Scholar
  82. Suetterlin KJ, Sayer AA (2014) Proprioception: where are we now? A commentary on clinical assessment, changes across the life course, functional implications and future interventions. Age Ageing 43:313–318CrossRefPubMedGoogle Scholar
  83. Sunagawa M et al (2017) Distinct development of the glycinergic terminals in the ventral and dorsal horns of the mouse cervical spinal cord. Neuroscience 343:459–471CrossRefPubMedGoogle Scholar
  84. Sutherland TC, Mathews KJ, Mao Y, Nguyen T, Gorrie CA (2016) Differences in the cellular response to acute spinal cord injury between developing and mature rats highlights the potential significance of the inflammatory response. Front Cell Neurosci 10:310PubMedGoogle Scholar
  85. Sykova E, Mazel T, Hasenohrl RU, Harvey AR, Simonova Z, Mulders WH, Huston JP (2002) Learning deficits in aged rats related to decrease in extracellular volume and loss of diffusion anisotropy in hippocampus. Hippocampus 12:269–279CrossRefPubMedGoogle Scholar
  86. Taves S, Berta T, Chen G, Ji RR (2013) Microglia and spinal cord synaptic plasticity in persistent pain. Neural Plast 2013:753656CrossRefPubMedPubMedCentralGoogle Scholar
  87. Thornell LE, Carlsson L, Eriksson PO, Liu JX, Osterlund C, Stal P, Pedrosa-Domellof F (2015) Fibre typing of intrafusal fibres. J Anat 227:136–156CrossRefPubMedPubMedCentralGoogle Scholar
  88. Todd AJ, Hughes DI, Polgar E, Nagy GG, Mackie M, Ottersen OP, Maxwell DJ (2003) The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal horn. Eur J Neurosci 17:13–27CrossRefPubMedGoogle Scholar
  89. Tomlinson BE, Irving D (1977) The numbers of limb motor neurons in the human lumbosacral cord throughout life. J Neurol Sci 34:213–219CrossRefPubMedGoogle Scholar
  90. Triolo D et al (2006) Loss of glial fibrillary acidic protein (GFAP) impairs Schwann cell proliferation and delays nerve regeneration after damage. J Cell Sci 119:3981–3993CrossRefPubMedGoogle Scholar
  91. Valdez G, Tapia JC, Kang H, Clemenson GD Jr, Gage FH, Lichtman JW, Sanes JR (2010) Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise. Proc Natl Acad Sci 107:14863–14868CrossRefPubMedGoogle Scholar
  92. van der Poel C, Gosselin LE, Schertzer JD, Ryall JG, Swiderski K, Wondemaghen M, Lynch GS (2011) Ageing prolongs inflammatory marker expression in regenerating rat skeletal muscles after injury. J Inflamm (Lond) 8:41CrossRefPubMedCentralGoogle Scholar
  93. VanGuilder HD, Yan H, Farley JA, Sonntag WE, Freeman WM (2010) Aging alters the expression of neurotransmission-regulating proteins in the hippocampal synaptoproteome. J Neurochem 113:1577–1588PubMedPubMedCentralGoogle Scholar
  94. Vaughan SK, Stanley OL, Valdez G (2017) Impact of aging on proprioceptive sensory neurons and intrafusal muscle fibers in mice. J Gerontol 72:771–779Google Scholar
  95. Watson C, Paxinos G, Kayalioglu G, Kayalioglu G, Christopher & Dana Reeve Foundation (2009) The spinal cord: a Christopher and Dana Reeve Foundation text and atlas, 1st edn. Elsevier/Academic Press, LondonGoogle Scholar
  96. Welniarz Q, Dusart I, Roze E (2017) The corticospinal tract: evolution, development, and human disorders. Dev Neurobiol 77:810–829CrossRefPubMedGoogle Scholar
  97. White Z, White RB, McMahon C, Grounds MD, Shavlakadze T (2016) High mTORC1 signaling is maintained, while protein degradation pathways are perturbed in old murine skeletal muscles in the fasted state. Int J Biochem Cell Biol 78:10–21CrossRefPubMedGoogle Scholar
  98. Wojcik SM et al (2004) An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size. Proc Natl Acad Sci 101:7158–7163CrossRefPubMedGoogle Scholar
  99. You SW et al (2016) Large-scale reconstitution of a retina-to-brain pathway in adult rats using gene therapy and bridging grafts: an anatomical and behavioral analysis. Exp Neurol 279:197–211CrossRefPubMedGoogle Scholar
  100. Zhu X, Ward PJ, English AW (2016) Selective requirement for maintenance of synaptic contacts onto motoneurons by target-derived trkB receptors. Neural Plast 2016:2371893CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.School of Human SciencesThe University of Western AustraliaPerthAustralia
  2. 2.Perron Institute for Neurological and Translational ScienceNedlandsAustralia

Personalised recommendations