1932

Abstract

I have been involved in two scientific discoveries of some impact. One is the discovery of long-term potentiation (LTP), the phenomenon that brief, high-frequency impulse activity at synapses in the brain can lead to long-lasting increases in their efficiency of transmission. This finding demonstrated that synapses are plastic, a property thought to be necessary for learning and memory. The other discovery is that nerve-evoked muscle impulse activity, rather than putative trophic factors, controls the properties of muscle fibers. Here I describe how these two discoveries were made, the unexpected difficulties of reproducing the first discovery, and the controversies that followed the second discovery. I discuss why the first discovery took many years to become generally recognized, whereas the second caused an immediate sensation and entered textbooks and major reviews but is now largely forgotten. In the long run, discovering a new phenomenon has greater impact than falsifying a popular hypothesis.

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2016-02-10
2024-06-25
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Literature Cited

  1. Lømo T. 1.  1966. Frequency potentiation of excitatory synaptic activity in the dentate area of the hippocampal formation. Acta Physiol. Scand. 68:Suppl. 277128 [Google Scholar]
  2. Lømo T, Rosenthal J. 2.  1972. Control of ACh sensitivity by muscle activity in the rat. J. Physiol. 221:2493–513 [Google Scholar]
  3. Lømo T, Mollica A. 3.  1962. Activity of single units in primary optic cortex of the unanaesthetized rabbit during visual, auditory, olfactory and painful stimulation. Arch. Ital. Biol. 100:86–120 [Google Scholar]
  4. Andersen P, Holmqvist B, Voorhoeve PE. 4.  1966. Excitatory synapses on hippocampal apical dendrites activated by entorhinal stimulation. Acta Physiol. Scand. 66:4461–72 [Google Scholar]
  5. Lømo T. 5.  1971. Patterns of activation in a monosynaptic cortical pathway: the perforant path input to the dentate area of the hippocampal formation. Exp. Brain Res. 12:118–45 [Google Scholar]
  6. Lømo T. 6.  1971. Potentiation of monosynaptic EPSPs in the perforant path–dentate granule cell synapse. Exp. Brain Res. 12:146–63 [Google Scholar]
  7. Lømo T. 7.  2009. Excitability changes within transverse lamellae of dentate granule cells and their longitudinal spread following orthodromic or antidromic activation. Hippocampus 19:7633–48 [Google Scholar]
  8. Bliss TVP. 8.  2003. A journey from neocortex to hippocampus. Philos. Trans. R. Soc. B 358:1432621–23 [Google Scholar]
  9. Andersen P, Bliss TV, Skrede KK. 9.  1971. Unit analysis of hippocampal population spikes. Exp. Brain Res. 13:2208–21 [Google Scholar]
  10. Andersen P, Bliss TV, Skrede KK. 10.  1971. Lamellar organization of hippocampal pathways. Exp. Brain Res. 13:2222–38 [Google Scholar]
  11. Sloviter RS, Lømo T. 11.  2012. Updating the lamellar hypothesis of hippocampal organization. Front. Neural Circuits 6:102 [Google Scholar]
  12. Bliss TV, Gardner-Medwin AR, Lømo T. 12.  1973. Synaptic plasticity in the hipoocampal formation. Macromolecules and Behaviour G Ansell, PB Bradley 193–203 London: Macmillan [Google Scholar]
  13. Bliss TV, Lømo T. 13.  1973. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. 232:2331–56 [Google Scholar]
  14. Nicoll RA. 14.  1995. Landmarks. J. NIH Res. 7:59–67 [Google Scholar]
  15. Bliss TV, Gardner-Medwin AR. 15.  1973. Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path. J. Physiol. 232:2357–74 [Google Scholar]
  16. Maggio N, Segal M. 16.  2010. Corticosteroid regulation of synaptic plasticity in the hippocampus. Sci. World J. 10:462–69 [Google Scholar]
  17. Fa M, Xia L, Anunu R, Kehat O, Kriebel M. 17.  et al. 2014. Stress modulation of hippocampal activity—spotlight on the dentate gyrus. Neurobiol. Learn. Mem. 112:53–60 [Google Scholar]
  18. Alfarez DN, Joëls M, Krugers HJ. 18.  2003. Chronic unpredictable stress impairs long-term potentiation in rat hippocampal CA1 area and dentate gyrus in vitro. Eur. J. Neurosci. 17:91928–34 [Google Scholar]
  19. Wang J, Akirav I, Richter-Levin G. 19.  2000. Short-term behavioral and electrophysiological consequences of underwater trauma. Physiol. Behav. 70:3–4327–32 [Google Scholar]
  20. Dolphin AC, Errington ML, Bliss TV. 20.  1982. Long-term potentiation of the perforant path in vivo is associated with increased glutamate release. Nature 297:5866496–98 [Google Scholar]
  21. Lømo T. 21.  2012. The History of Neuroscience in Autobiography 7 New York: Oxford Univ. Press55 [Google Scholar]
  22. Douglas RM, Goddard GV. 22.  1975. Long-term potentiation of the perforant path–granule cell synapse in the rat hippocampus. Brain Res. 86:2205–15 [Google Scholar]
  23. Schwartzkroin PA, Wester K. 23.  1975. Long-lasting facilitation of a synaptic potential following tetanization in the in vitro hippocampal slice. Brain Res. 89:1107–19 [Google Scholar]
  24. Alger BE, Teyler TJ. 24.  1976. Long-term and short-term plasticity in the CA1, CA3, and dentate regions of the rat hippocampal slice. Brain Res. 110:3463–80 [Google Scholar]
  25. Andersen P, Sundberg SH, Sveen O, Wigström H. 25.  1977. Specific long-lasting potentiation of synaptic transmission in hippocampal slices. Nature 266:5604736–37 [Google Scholar]
  26. McNaughton BL, Douglas RM, Goddard GV. 26.  1978. Synaptic enhancement in fascia dentata: cooperativity among coactive afferents. Brain Res. 157:2277–93 [Google Scholar]
  27. McNaughton BL. 27.  1982. Long-term synaptic enhancement and short-term potentiation in rat fascia dentata act through different mechanisms. J. Physiol. 324:249–62 [Google Scholar]
  28. Kandel ER, Schwartz JH. 28.  1981. Principles of Neural Science New York/Amsterdam/Oxford, UK: Elsevier/North-Holland [Google Scholar]
  29. Brodal A. 29.  1981. Neurological Anatomy in Relation to Clinical Medicine. New York: Oxford Univ. Press, 3rd ed.. [Google Scholar]
  30. Lynch G. 30.  2003. Long-term potentiation in the Eocene. Philos. Trans. R. Soc. B 358:1432625–28 [Google Scholar]
  31. Eccles JC. 31.  1970. Facing Reality: Philosophical Adventures by a Brain Scientist New York/Berlin/Heidelberg, Ger: Springer-Verlag [Google Scholar]
  32. Collingridge GL, Kehl SJ, McLennan H. 32.  1983. Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. J. Physiol. 334:33–46 [Google Scholar]
  33. Lynch G, Larson J, Kelso S, Barrionuevo G, Schottler F. 33.  1983. Intracellular injections of EGTA block induction of hippocampal long-term potentiation. Nature 305:5936719–21 [Google Scholar]
  34. Morris RG, Anderson E, Lynch GS, Baudry M. 34.  1986. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-d-aspartate receptor antagonist, AP5. Nature 319:6056774–76 [Google Scholar]
  35. Skrede KK, Westgaard RH. 35.  1971. The transverse hippocampal slice: a well-defined cortical structure maintained in vitro. Brain Res. 35:2589–93 [Google Scholar]
  36. Andersen P. 36.  1960. Interhippocampal impulses. II. Apical dendritic activation of CA1 neurons. Acta Physiol. Scand. 48:2178–208 [Google Scholar]
  37. Andersen P. 37.  1960. Interhippocampal impulses. III. Basal dendritic activation of CA3 neurons. Acta Physiol. Scand. 48:2209–30 [Google Scholar]
  38. Black AH. 38.  1975. Hippocampal electrical activity and behavior. The Hippocampus 2 RL Isaacson, KH Pribham 129–67 Boston, MA: Springer [Google Scholar]
  39. Horel JA. 39.  1978. The neuroanatomy of amnesia. A critique of the hippocampal memory hypothesis. Brain 101:3403–45 [Google Scholar]
  40. Scoville WB, Milner B. 40.  1957. Loss of recent memory after bilateral hippocampal lesions. J. Neurol. Neurosurg. Psychiatr. 20:111–21 [Google Scholar]
  41. Annese J, Schenker-Ahmed NM, Bartsch H, Maechler P, Sheh C. 41.  et al. 2014. Postmortem examination of patient H.M.'s brain based on histological sectioning and digital 3D reconstruction. Nat. Commun. 5:3122 [Google Scholar]
  42. Lisman J, Lichtman JW, Sanes JR. 42.  2003. LTP: perils and progress. Nat. Rev. Neurosci. 4:11926–29 [Google Scholar]
  43. Gallistel CR, Matzel LD. 43.  2013. The neuroscience of learning: beyond the Hebbian synapse. Annu. Rev. Psychol. 64:169–200 [Google Scholar]
  44. Madroñal N, Gruart A, Sacktor TC, Delgado-García JM. 44.  2010. PKMζ inhibition reverses learning-induced increases in hippocampal synaptic strength and memory during trace eyeblink conditioning. PLOS ONE 5:4e10400 [Google Scholar]
  45. Cooke SF, Bear MF. 45.  2010. Visual experience induces long-term potentiation in the primary visual cortex. J. Neurosci. 30:4816304–13 [Google Scholar]
  46. Sacktor TC. 46.  2011. How does PKMζ maintain long-term memory?. Nat. Rev. Neurosci. 12:19–15 [Google Scholar]
  47. Glanzman DL. 47.  2013. PKM and the maintenance of memory. F1000 Biol. Rep. 5:44 [Google Scholar]
  48. Shema R, Sacktor TC, Dudai Y. 48.  2007. Rapid erasure of long-term memory associations in the cortex by an inhibitor of PKMζ. Science 317:5840951–53 [Google Scholar]
  49. Lee AM, Kanter BR, Wang D, Lim JP, Zou ME. 49.  et al. 2013. Prkcz null mice show normal learning and memory. Nature 493:7432416–19 [Google Scholar]
  50. Volk LJ, Bachman JL, Johnson R, Yu Y, Huganir RL. 50.  2013. PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory. Nature 493:7432420–23 [Google Scholar]
  51. Cooke SF, Bear MF. 51.  2014. How the mechanisms of long-term synaptic potentiation and depression serve experience-dependent plasticity in primary visual cortex. Philos. Trans. R. Soc. B 369:163320130284 [Google Scholar]
  52. Moser EI, Krobert KA, Moser MB, Morris RG. 52.  1998. Impaired spatial learning after saturation of long-term potentiation. Science 281:53852038–42 [Google Scholar]
  53. Rioult-Pedotti MS, Friedman D, Donoghue JP. 53.  2000. Learning-induced LTP in neocortex. Science 290:5491533–36 [Google Scholar]
  54. Cantarero G, Lloyd A, Celnik P. 54.  2013. Reversal of long-term potentiation–like plasticity processes after motor learning disrupts skill retention. J. Neurosci. 33:3112862–69 [Google Scholar]
  55. Cantarero G, Tang B, O'Malley R, Salas R, Celnik P. 55.  2013. Motor learning interference is proportional to occlusion of LTP-like plasticity. J. Neurosci. 33:114634–41 [Google Scholar]
  56. Taylor AM, Bus T, Sprengel R, Seeburg PH, Rawlins JNP, Bannerman DM. 56.  2014. Hippocampal NMDA receptors are important for behavioural inhibition but not for encoding associative spatial memories. Philos. Trans. R. Soc. B 369:163320130149 [Google Scholar]
  57. Tower SS. 57.  1937. Trophic control of non-nervous tissues by the nervous system: a study of muscle and bone innervated from an isolated and quiescent region of spinal cord. J. Comp. Neurol. 67:2241–67 [Google Scholar]
  58. Langley JN, Kato T. 58.  1915. The rate of loss of weight in skeletal muscle after nerve section with some observations on the effect of stimulation and other treatment. J. Physiol. 49:5432–40 [Google Scholar]
  59. Langley JN. 59.  1916. Observations on denervated muscle. J. Physiol. 50:5335–44 [Google Scholar]
  60. Miledi R. 60.  1960. Junctional and extra-junctional acetylcholine receptors in skeletal muscle fibres. J. Physiol. 151:24–30 [Google Scholar]
  61. Miledi R. 61.  1960. The acetylcholine sensitivity of frog muscle fibres after complete or partial devervation. J. Physiol. 151:1–23 [Google Scholar]
  62. Johns TR, Thesleff S. 62.  1961. Effects of motor inactivation on the chemical sensitivity of skeletal muscle. Acta Physiol. Scand. 51:2–3136–41 [Google Scholar]
  63. Thesleff S. 63.  1960. Supersensitivity of skeletal muscle produced by botulinum toxin. J. Physiol. 151:598–607 [Google Scholar]
  64. Luco JV, Eyzaguirre C. 64.  1955. Fibrillation and hypersensitivity to ACh in denervated muscle: effect of length of degenerating nerve fibers. J. Neurophysiol. 18:165–73 [Google Scholar]
  65. Eccles SJC. 65.  1964. The Physiology of Synapses Berlin/Göttingen/Heidelberg, Ger: Springer [Google Scholar]
  66. Buller AJ, Eccles JC, Eccles RM. 66.  1960. Interactions between motoneurones and muscles in respect of the characteristic speeds of their responses. J. Physiol. 150:417–39 [Google Scholar]
  67. Eccles JC, Eccles RM, Kozak W. 67.  1962. Further investigations on the influence of motoneurones on the speed of muscle contraction. J. Physiol. 163:2324–39 [Google Scholar]
  68. Robert ED, Oester YT. 68.  1970. Absence of supersensitivity to acetylcholine in innervated muscle subjected to a prolonged pharmacologic nerve block. J. Pharmacol. Exp. Ther. 174:1133–40 [Google Scholar]
  69. Lømo T, Westgaard RH. 69.  1976. Control of ACh sensitivity in rat muscle fibers. Cold Spring Harb. Symp. Quant. Biol. 40:263–74 [Google Scholar]
  70. Lømo T, Westgaard RH. 70.  1975. Further studies on the control of ACh sensitivity by muscle activity in the rat. J. Physiol. 252:3603–26 [Google Scholar]
  71. Westgaard RH. 71.  1975. Influence of activity on the passive electrical properties of denervated soleus muscle fibres in the rat. J. Physiol. 251:3683–97 [Google Scholar]
  72. Lømo T, Westgaard RH, Dahl HA. 72.  1974. Contractile properties of muscle: control by pattern of muscle activity in the rat. Proc. R. Soc. B 187:108699–103 [Google Scholar]
  73. Westgaard RH, Lømo T. 73.  1988. Control of contractile properties within adaptive ranges by patterns of impulse activity in the rat. J. Neurosci. 8:124415–26 [Google Scholar]
  74. Hennig R, Lømo T. 74.  1987. Effects of chronic stimulation on the size and speed of long-term denervated and innervated rat fast and slow skeletal muscles. Acta Physiol. Scand. 130:1115–31 [Google Scholar]
  75. Ausoni S, Gorza L, Schiaffino S, Gundersen K, Lømo T. 75.  1990. Expression of myosin heavy chain isoforms in stimulated fast and slow rat muscles. J. Neurosci. 10:1153–60 [Google Scholar]
  76. Eken T, Gundersen K. 76.  1988. Electrical stimulation resembling normal motor-unit activity: effects on denervated fast and slow rat muscles. J. Physiol. 402:651–69 [Google Scholar]
  77. Gundersen K, Eken T. 77.  1992. The importance of frequency and amount of electrical stimulation for contractile properties of denervated rat muscles. Acta Physiol. Scand. 145:149–57 [Google Scholar]
  78. Deshpande SS, Albuquerque EX, Guth L. 78.  1976. Neurotrophic regulation of prejunctional and postjunctional membrane at the mammalian motor endplate. Exp. Neurol. 53:1151–65 [Google Scholar]
  79. Gutmann E. 79.  1976. Neurotrophic relations. Annu. Rev. Physiol. 38:177–216 [Google Scholar]
  80. Jolesz F, Sreter FA. 80.  1981. Development, innervation, and activity-pattern induced changes in skeletal muscle. Annu. Rev. Physiol. 43:531–52 [Google Scholar]
  81. Witzemann V, Brenner HR, Sakmann B. 81.  1991. Neural factors regulate AChR subunit mRNAs at rat neuromuscular synapses. J. Cell Biol. 114:1125–41 [Google Scholar]
  82. Grinnell AD. 82.  1994. Trophic interaction between nerve and muscle. Myology: Basic and Clinical 1 AG Engel, C Franzini-Armstrong 303–32 New York: McGraw-Hill, 2nd ed.. [Google Scholar]
  83. Nicholls JG, Martin AR, Wallace BG, Fuchs PA. 83.  2001. From Neuron to Brain Sunderland, MA: Sinauer, 4th ed.. [Google Scholar]
  84. Connor EA, McMahan UJ. 84.  1987. Cell accumulation in the junctional region of denervated muscle. J. Cell Biol. 104:1109–20 [Google Scholar]
  85. Murray MA, Robbins N. 85.  1982. Cell proliferation in denervated muscle: identity and origin of dividing cells. Neuroscience 7:71823–33 [Google Scholar]
  86. Murray MA, Robbins N. 86.  1982. Cell proliferation in denervated muscle: time course, distribution and relation to disuse. Neuroscience 7:71817–22 [Google Scholar]
  87. Jones R, Vrbová G. 87.  1974. Two factors responsible for the development of denervation hypersensitivity. J. Physiol. 236:3517–38 [Google Scholar]
  88. Pasino E, Buffelli M, Busetto G, Cangiano A. 88.  1997. Use of dexamethasone with TTX block of nerve conduction shows that muscle membrane properties are fully controlled by evoked activity. Brain Res. 770:1–2242–47 [Google Scholar]
  89. Buffelli M, Pasino E, Cangiano A. 89.  1997. Paralysis of rat skeletal muscle equally affects contractile properties as does permanent denervation. J. Muscle Res. Cell Motil. 18:6683–95 [Google Scholar]
  90. Cangiano A, Lutzemberger L. 90.  1977. Partial denervation affects both denervated and innervated fibers in the mammalian skeletal muscle. Science 196:4289542–45 [Google Scholar]
  91. Cangiano A, Lutzemberger L. 91.  1980. Partial denervation in inactive muscle affects innervated and de-nervated fibres equally. Nature 285:5762233–35 [Google Scholar]
  92. Pasino E, Buffelli M, Arancio O, Busetto G, Salviati A, Cangiano A. 92.  1996. Effects of long-term conduction block on membrane properties of reinnervated and normally innervated rat skeletal muscle. J. Physiol. 497:2457–72 [Google Scholar]
  93. Miledi R, Slater CR. 93.  1970. On the degeneration of rat neuromuscular junctions after nerve section. J. Physiol. 207:2507–28 [Google Scholar]
  94. Albuquerque EX, Warnick JE, Tasse JR, Sansone FM. 94.  1972. Effects of vinblastine and colchicine on neural regulation of the fast and slow skeletal muscles of the rat. Exp. Neurol. 37:3607–34 [Google Scholar]
  95. Hofmann WW, Thesleff S. 95.  1972. Studies on the trophic influence of nerve on skeletal muscle. Eur. J. Pharmacol. 20:3256–60 [Google Scholar]
  96. Cangiano A. 96.  1973. Acetylcholine supersensitivity: the role of neurotrophic factors. Brain Res. 58:1255–59 [Google Scholar]
  97. Lømo T. 97.  1974. Neurotrophic control of colchicine effects on muscle?. Nature 249:456473–74 [Google Scholar]
  98. McMahan UJ. 98.  1990. The agrin hypothesis. Cold Spring Harb. Symp. Quant. Biol. 55:407–18 [Google Scholar]
  99. Thoenen H, Edgar D. 99.  1985. Neurotrophic factors. Science 229:4710238–42 [Google Scholar]
  100. Fitzsimonds RM, Poo MM. 100.  1998. Retrograde signaling in the development and modification of synapses. Physiol. Rev. 78:1143–70 [Google Scholar]
  101. Lewin GR, Barde YA. 101.  1996. Physiology of the neurotrophins. Annu. Rev. Neurosci. 19:289–317 [Google Scholar]
  102. Oppenheim RW. 102.  1996. Neurotrophic survival molecules for motoneurons: an embarrassment of riches. Neuron 17:2195–97 [Google Scholar]
  103. Park H, Poo M-M. 103.  2013. Neurotrophin regulation of neural circuit development and function. Nat. Rev. Neurosci. 14:17–23 [Google Scholar]
  104. Lu H, Park H, Poo M-M. 104.  2014. Spike-timing-dependent BDNF secretion and synaptic plasticity. Philos. Trans. R. Soc. B 369:163320130132 [Google Scholar]
  105. Pette D, Smith ME, Staudte HW, Vrbová G. 105.  1973. Effects of long-term electrical stimulation on some contractile and metabolic characteristics of fast rabbit muscles. Pflüg. Arch. 338:3257–72 [Google Scholar]
  106. Salmons S, Sreter FA. 106.  1976. Significance of impulse activity in the transformation of skeletal muscle type. Nature 263:557230–34 [Google Scholar]
  107. Eerbeek O, Kernell D, Verhey BA. 107.  1984. Effects of fast and slow patterns of tonic long-term stimulation on contractile properties of fast muscle in the cat. J. Physiol. 352:73–90 [Google Scholar]
  108. Purves D, Sakmann B. 108.  1974. The effect of contractile activity on fibrillation and extrajunctional acetylcholine-sensitivity in rat muscle maintained in organ culture. J. Physiol. 237:1157–82 [Google Scholar]
  109. Hennig R, Lømo T. 109.  1985. Firing patterns of motor units in normal rats. Nature 314:6007164–66 [Google Scholar]
  110. Sacheck JM, Hyatt J-PK, Raffaello A, Jagoe RT, Roy RR. 110.  et al. 2007. Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. FASEB J. 21:1140–55 [Google Scholar]
  111. Hyatt J-PK, Roy RR, Baldwin KM, Edgerton VR. 111.  2003. Nerve activity–independent regulation of skeletal muscle atrophy: role of MyoD and myogenin in satellite cells and myonuclei. Am. J. Physiol. Cell Physiol. 285:5C1161–73 [Google Scholar]
  112. Hyatt J-PK, Roy RR, Baldwin KM, Wernig A, Edgerton VR. 112.  2006. Activity-unrelated neural control of myogenic factors in a slow muscle. Muscle Nerve 33:149–60 [Google Scholar]
  113. McCullagh KJA, Calabria E, Pallafacchina G, Ciciliot S, Serrano AL. 113.  et al. 2004. NFAT is a nerve activity sensor in skeletal muscle and controls activity-dependent myosin switching. PNAS 101:2910590–95 [Google Scholar]
  114. Tothova J, Blaauw B, Pallafacchina G, Rudolf R, Argentini C. 114.  et al. 2006. NFATc1 nucleocytoplasmic shuttling is controlled by nerve activity in skeletal muscle. J. Cell Sci. 119:81604–11 [Google Scholar]
  115. Lømo T, Westgaard RH, Hennig R, Gundersen K. 115.  1985. The response of denervated muscle to long-term electrical stimulation. Reprinted in 2014 in Eur. J. Trans. Myol.. Basic Appl. Myol. 24:121–25 [Google Scholar]
  116. Kern H, Boncompagni S, Rossini K, Mayr W, Fanò G. 116.  et al. 2004. Long-term denervation in humans causes degeneration of both contractile and excitation-contraction coupling apparatus, which is reversible by functional electrical stimulation (FES): a role for myofiber regeneration?. J. Neuropathol. Exp. Neurol. 63:9919–31 [Google Scholar]
  117. Boncompagni S, Kern H, Rossini K, Hofer C, Mayr W. 117.  et al. 2007. Structural differentiation of skeletal muscle fibers in the absence of innervation in humans. PNAS 104:4919339–44 [Google Scholar]
  118. Kern H, Carraro U, Adami N, Biral D, Hofer C. 118.  et al. 2010. Home-based functional electrical stimulation rescues permanently denervated muscles in paraplegic patients with complete lower motor neuron lesion. Neurorehabil. Neural Repair 24:8709–21 [Google Scholar]
  119. Younkin SG, Brett RS, Davey B, Younkin L. 119.  1978. Substances moved by axonal transport and released by nerve stimulation have an innervation-like effect on muscle. Science 200:43471292–95 [Google Scholar]
  120. Stent GS. 120.  1972. Prematurity and uniqueness in scientic discovery. Sci. Am. 227:84–93 [Google Scholar]
  121. Popper K. 121.  1976. Unended Quest: An Intellectual Autobiography London: Fontana/Collins [Google Scholar]
  122. Stent GS. 122.  1975. Limits to the scientific understanding of man. Science 187:41811052–57 [Google Scholar]
  123. Sinclair DC. 123.  1955. Cutaneous sensation and the doctrine of specific energy. Brain 78:4584–614 [Google Scholar]
  124. Weddell G. 124.  1955. Somesthesis and the chemical senses. Annu. Rev. Psychol. 6:119–36 [Google Scholar]
  125. Melzack R, Wall PD. 125.  1965. Pain mechanisms: a new theory. Science 150:3699971–79 [Google Scholar]
  126. Dimond EG, Kittle CF, Crockett JE. 126.  1960. Comparison of internal mammary artery ligation and sham operation for angina pectoris. Am. J. Cardiol. 5:483–86 [Google Scholar]
  127. Harrington A. 127.  2008. The Cure Within New York/London: W. W. Norton & Co. [Google Scholar]
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