Altered Functionality, Morphology, and Vesicular Glutamate Transporter Expression of Cortical Motor Neurons from a Presymptomatic Mouse Model of Amyotrophic Lateral Sclerosis

Cerebral Cortex

Volumn 26, Issue 4, 2016, Pages 1512-1528

  Saba, L ^a   Viscomi, M T ^a   Caioli, S ^a   Pignataro, A ^a   Bisicchia, E ^a   Pieri, M ^b   Molinari, M ^a   Ammassari Teule, M ^a,c   Zona, C ^a,b  

^a IRCCS FONDAZIONE SANTA LUCIA   (Italy)

^b UNIVERSITY OF ROME TOR VERGATA   (Italy)

^c CNR   (Italy)

Author keywords

excitatory neurotransmission; G93A mice; motor neuron hyperexcitability; neuronal morphology; vesicular glutamate transporter

Indexed keywords

BIOCYTIN; VESICULAR GLUTAMATE TRANSPORTER 2; COPPER ZINC SUPEROXIDE DISMUTASE; G9A PROTEIN, MOUSE; HISTONE LYSINE METHYLTRANSFERASE; SLC17A6 PROTEIN, MOUSE; SOD1 PROTEIN, HUMAN;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL EXPERIMENT; ARTICLE; CLINICAL FEATURE; CONTROLLED STUDY; CORTEX LAYER V; DENSITOMETRY; EXCITATORY POSTSYNAPTIC POTENTIAL; MALE; MEMBRANE STEADY POTENTIAL; MOTONEURON; MOTOR CORTEX; MOUSE; NEUROTRANSMISSION; NONHUMAN; PATHOGENESIS; PRIMARY MOTOR CORTEX; PRIORITY JOURNAL; PROTEIN EXPRESSION; PYRAMIDAL NERVE CELL; REAL TIME POLYMERASE CHAIN REACTION; WHOLE CELL PATCH CLAMP; ACTION POTENTIAL; ANIMAL; DENDRITE; DISEASE MODEL; GENETICS; HUMAN; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; SYNAPSE; TRANSGENIC MOUSE;

ACTION POTENTIALS; AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; DENDRITES; DISEASE MODELS, ANIMAL; EXCITATORY POSTSYNAPTIC POTENTIALS; HISTONE-LYSINE N-METHYLTRANSFERASE; HUMANS; MALE; MICE; MICE, TRANSGENIC; MOTOR CORTEX; MOTOR NEURONS; SUPEROXIDE DISMUTASE-1; SYNAPSES; VESICULAR GLUTAMATE TRANSPORT PROTEIN 2;

EID: 84963830474     PISSN: 10473211     EISSN: 14602199     Source Type: Journal    
DOI: 10.1093/cercor/bhu317     Document Type: Article

References (95)

1. Agis-Balboa RC, Pinna G, Zhubi A, Maloku E, Veldic M, Costa E, Guidotti A. 2006. Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis. Proc Natl Acad Sci USA. 103:14602-14607.
2. Alexianu ME, Kozovska M, Appel SH. 2001. Immune reactivity in a mouse model of familial ALS correlates with disease progression. Neurology. 57:1282-1289.
3. Amendola J, Durand J. 2008. Morphological differences between wild-type and transgenic superoxide dismutase 1 lumbarmotoneurons in postnatal mice. J Comp Neurol. 511:329-341.
4. Andersen PM. 2006. Amyotrophic lateral sclerosis associated with mutations in the CuZn superoxide dismutase gene. Curr Neurol Neurosci Rep. 6:37-46.
5. Barroso-Chinea P, Castle M, Aymerich MS, Perez-Manso M, Erro E, Tunon T, Lanciego JL. 2007. Expression of the mRNAs encoding for the vesicular glutamate transporters 1 and 2 in the rat thalamus. J Comp Neurol. 501:703-715.
6. Beauchamp C, Fridovich I. 1971. Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem. 44:276-287.
7. Bellingham MC. 2011. A review of the neural mechanisms of action and clinical efficiency of riluzole in treating amyotrophic lateral sclerosis: what havewe learned in the last decade? CNS Neurosci Ther. 17:4-31.
8. Boehmer G, GreffrathW, Martin E, Hermann S. 2000. Subthreshold oscillation of the membrane potential in magnocellular neurones of the rat supraoptic nucleus. J Physiol. 526(Pt 1):115-128.
9. Bogaert E, d'Ydewalle C, Van Den Bosch L. 2010. Amyotrophic lateral sclerosis and excitotoxicity: from pathological mechanism to therapeutic target. CNS Neurol Disord Drug Targets. 9:297-304.
10. Bruijn LI, Becher MW, Lee MK, Anderson KL, Jenkins NA, Copeland NG, Sisodia SS, Rothstein JD, Borchelt DR, Price DL, et al. 1997. ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron. 18:327-338.
11. Carunchio I, Curcio L, Pieri M, Pica F, Caioli S, Viscomi MT, MolinariM, Canu N, Bernardi G, Zona C. 2010. Increased levels of p70S6 phosphorylation in the G93A mouse model of amyotrophic lateral sclerosis and in valine-exposed cortical neurons in culture. Exp Neurol. 226:218-230.
12. Cepeda C, Starling AJ, Wu N, Nguyen OK, Uzgil B, Soda T, Andre VM, Ariano MA, Levine MS. 2004. Increased GABAergic function in mouse models of Huntington's disease: reversal by BDNF. J Neurosci Res. 78:855-867.
13. Cheah BC, Vucic S, Krishnan AV, KiernanMC. 2010. Riluzole, neuroprotection and amyotrophic lateral sclerosis. Curr Med Chem. 17:1942-1959.
14. Cline H. 2005. Synaptogenesis: A balancing act between excitation and inhibition. Curr Biol. 15:R203-R205.
15. de Carvalho M, Pinto S, Costa J, Evangelista T, Ohana B, Pinto A. 2010. A randomized, placebo-controlled trial of memantine for functional disability in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 11:456-460.
16. Deng HX, Hentati A, Tainer JA, Iqbal Z, Cayabyab A, Hung WY, Getzoff ED, Hu P, Herzfeldt B, Roos RP, et al. 1993. Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase. Science. 261:1047-1051.
17. Do MT, Bean BP. 2003. Subthreshold sodium currents and pacemaking of subthalamic neurons: modulation by slow inactivation. Neuron. 39:109-120.
18. Eastwood SL, Harrison PJ. 2005. Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons. Schizophr Res. 73:159-172.
19. Erickson JD, De Gois S, Varoqui H, Schafer MK, Weihe E. 2006. Activity-dependent regulation of vesicular glutamate and GABA transporters: A means to scale quantal size. Neurochem Int. 48:643-649.
20. Foran E, Bogush A, Goffredo M, Roncaglia P, Gustincich S, Pasinelli P, Trotti D. 2011. Motor neuron impairment mediated by a sumoylated fragment of the glial glutamate transporter EAAT2. Glia. 59:1719-1731.
21. Foran E, Trotti D. 2009. Glutamate transporters and the excitotoxic path to motor neuron degeneration in amyotrophic lateral sclerosis. Antioxid Redox Signal. 11:1587-1602.
22. Franklin KJ, Paxinos G. 1997. The Mouse Brain in Stereotaxic Coordinates. San Diego: Academic Press.
23. Fremeau RT, KamK, Qureshi T, Johnson J, Copenhagen DR, Storm-Mathisen J, Chaudhry FA, Nicoll RA, Edwards RH. 2004. Vesicular glutamate transporters 1 and 2 target to functionally distinct synaptic release sites. Science. 304:1815-1819.
24. Fremeau RT, TroyerMD, Pahner I, Nygaard GO, Tran CH, Reimer RJ, Bellocchio EE, Fortin D, Storm-Mathisen J, Edwards RH. 2001. The expression of vesicular glutamate transporters defines two classes of excitatory synapse. Neuron. 31:247-260.
25. Fremeau RT, Voglmaier S, Seal RP, Edwards RH. 2004. VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate. Trends Neurosci. 27:98-103.
26. Frizzo ME, Dall'Onder LP, Dalcin KB, Souza DO. 2004. Riluzole enhances glutamate uptake in rat astrocyte cultures. Cell Mol Neurobiol. 24:123-128.
27. Fujiyama F, Furuta T, Kaneko T. 2001. Immunocytochemical localization of candidates for vesicular glutamate transporters in the rat cerebral cortex. J Comp Neurol. 435:379-387.
28. Gordon PH. 2011. Amyotrophic lateral sclerosis: pathophysiology, diagnosis and management. CNS Drugs. 25:1-15.
29. Graziano A, Liu XB, Murray KD, Jones EG. 2008. Vesicular glutamate transporters define two sets of glutamatergic afferents to the somatosensory thalamus and two thalamocortical projections in the mouse. J Comp Neurol. 507: 1258-1276.
30. Grosskreutz J, Haastert K, Dewil M, Van Damme P, Callewaert G, Robberecht W, Dengler R, Van Den Bosch L. 2007. Role of mitochondria in kainate-induced fast Ca2+ transients in cultured spinal motor neurons. Cell Calcium. 42:59-69.
31. Guatteo E, Carunchio I, Pieri M, Albo F, Canu N, Mercuri NB, Zona C. 2007. Altered calcium homeostasis in motor neurons following AMPA receptor but not voltage-dependent calcium channels' activation in a genetic model of amyotrophic lateral sclerosis. Neurobiol Dis. 28:90-100.
32. Gurney ME. 1994. Transgenic-mouse model of amyotrophic lateral sclerosis. N Engl J Med. 331:1721-1722.
33. Harris KM, Fiala JC, Ostroff L. 2003. Structural changes at dendritic spine synapses during long-term potentiation. Philos Trans R Soc Lond B Biol Sci. 358:745-748.
34. Hooks BM, Mao T, Gutnisky DA, Yamawaki N, Svoboda K, Shepherd GM. 2013. Organization of cortical and thalamic input to pyramidal neurons in mouse motor cortex. J Neurosci. 33:748-760.
35. Kashani A, Betancur C, Giros B, Hirsch E, El Mestikawy S. 2007. Altered expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in Parkinson disease. Neurobiol Aging. 28:568-578.
36. Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, Burrell JR, Zoing MC. 2011. Amyotrophic lateral sclerosis. Lancet. 377:942-955.
37. Kim HJ, Kim TH, Choi SJ, Hong YJ, Yang JS, Sung KW, Rhie DJ, Hahn SJ, Yoon SH. 2012. Fluoxetine suppresses synaptically induced [Ca(2)(+)]i spikes and excitotoxicity in cultured rat hippocampal neurons. Brain Res. 1490:23-34.
38. Kirvell SL, Esiri M, Francis PT. 2006. Down-regulation of vesicular glutamate transporters precedes cell loss and pathology in Alzheimer's disease. J Neurochem. 98:939-950.
39. Kuo JJ, Siddique T, Fu R, Heckman CJ. 2005. Increased persistent Na(+) current and its effect on excitability in motoneurones cultured from mutant SOD1 mice. J Physiol. 563:843-854.
40. Levin SI, Khaliq ZM, Aman TK, Grieco TM, Kearney JA, Raman IM, Meisler MH. 2006. Impaired motor function in mice with cellspecific knockout of sodium channel Scn8a (NaV1.6) in cerebellar purkinje neurons and granule cells. J Neurophysiol. 96:785-793.
41. Libersat F, Duch C. 2004. Mechanisms of dendritic maturation. Mol Neurobiol. 29:303-320.
42. Lin CL, Bristol LA, Jin L, Dykes-Hoberg M, Crawford T, Clawson L, Rothstein JD. 1998. Aberrant RNA processing in a neurodegenerative disease: The cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Neuron. 20:589-602.
43. Maekawa S, Al-Sarraj S, Kibble M, Landau S, Parnavelas J, Cotter D, Everall I, Leigh PN. 2004. Cortical selective vulnerability in motor neuron disease: A morphometric study. Brain. 127:1237-1251.
44. Martorana F, Brambilla L, Valori CF, Bergamaschi C, Roncoroni C, Aronica E, Volterra A, Bezzi P, Rossi D. 2012. The BH4 domain of Bcl-X(L) rescues astrocyte degeneration in amyotrophic lateral sclerosis by modulating intracellular calcium signals. Hum Mol Genet. 21:826-840.
45. Miller RG, Mitchell JD, Moore DH. 2012. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 3:CD001447.
46. Mintz IM, Sabatini BL, Regehr WG. 1995. Calcium control of transmitter release at a cerebellar synapse. Neuron. 15:675-688.
47. Moechars D, Weston MC, Leo S, Callaerts-Vegh Z, Goris I, Daneels G, Buist A, Cik M, van der Spek P, Kass S, et al. ' 2006. Vesicular glutamate transporter VGLUT2 expression levels control quantal size and neuropathic pain. J Neurosci. 26:12055-12066.
48. Mogyoros I, Kiernan MC, Burke D. 1996. Strength-duration properties of human peripheral nerve. Brain. 119(Pt 2): 439-447.
49. Mogyoros I, Kiernan MC, Burke D, Bostock H. 1998. Strength-duration properties of sensory and motor axons in amyotrophic lateral sclerosis. Brain. 121(Pt 5):851-859.
50. Moreira LG, Pereira LC, Drummond PR, De Mesquita JF. 2013. Structural and functional analysis of human SOD1 in amyotrophic lateral sclerosis. PLoS One. 8:e81979.
51. Morel L, Regan M, Higashimori H, Ng SK, Esau C, Vidensky S, Rothstein J, Yang Y. 2013. Neuronal exosomal miRNAdependent translational regulation of astroglial glutamate transporter GLT1. J Biol Chem. 288:7105-7116.
52. Moutsimilli L, Farley S, Dumas S, El Mestikawy S, Giros B, Tzavara ET. 2005. Selective cortical VGLUT1 increase as a marker for antidepressant activity. Neuropharmacology. 49:890-900.
53. Moutsimilli L, Farley S, El Khoury MA, Chamot C, Sibarita JB, Racine V, El Mestikawy S, Mathieu F, Dumas S, Giros B, et al. 2008. Antipsychotics increase vesicular glutamate transporter 2 (VGLUT2) expression in thalamolimbic pathways. Neuropharmacology. 54:497-508.
54. Nieto-Gonzalez JL, Moser J, Lauritzen M, Schmitt-John T, Jensen K. 2010. Reduced GABAergic inhibition explains cortical hyperexcitability in the wobbler mouse model of ALS. Cereb Cortex. 21:625-635.
55. Oswald MJ, Tantirigama ML, Sonntag I, Hughes SM, Empson RM. 2013. Diversity of layer 5 projection neurons in the mouse motor cortex. Front Cell Neurosci. 7:174.
56. Pamphlett R, Todd E, Vink R, McQuilty R, Cheema SS. 2003. Magnesium supplementation does not delay disease onset or increase survival in a mouse model of familial ALS. J Neurol Sci. 216:95-98.
57. Panov A, Kubalik N, Zinchenko N, Hemendinger R, Dikalov S, Bonkovsky HL. 2011. Respiration and ROS production in brain and spinal cord mitochondria of transgenic rats with mutant G93a Cu/Zn-superoxide dismutase gene. Neurobiol Dis. 44:53-62.
58. Petersen CC, Crochet S. 2013. Synaptic computation and sensory processing in neocortical layer 2/3. Neuron. 78:28-48.
59. Philips T, RobberechtW. 2011. Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol. 10:253-263.
60. Pieri M, Albo F, Gaetti C, Spalloni A, Bengtson CP, Longone P, Cavalcanti S, Zona C. 2003. Altered excitability of motor neurons in a transgenic mouse model of familial amyotrophic lateral sclerosis. Neurosci Lett. 351:153-156.
61. Pieri M, Caioli S, Canu N, Mercuri NB, Guatteo E, Zona C. 2013. Over-expression of N-type calcium channels in cortical neurons from a mouse model of amyotrophic lateral sclerosis. Exp Neurol. 247:349-358.
62. Pieri M, Carunchio I, Curcio L, Mercuri NB, Zona C. 2009. Increased persistent sodium current determines cortical hyperexcitability in a genetic model of amyotrophic lateral sclerosis. Exp Neurol. 215:368-379.
63. Qian J, Noebels JL. 2001. Presynaptic Ca2+ channels and neurotransmitter release at the terminal of a mouse cortical neuron. J Neurosci. 21:3721-3728.
64. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J,O'Regan JP, Deng HX, et al. 1993.Mutations in Cu/Zn superoxide dismutase gene are associatedwith familial amyotrophic lateral sclerosis. Nature. 362:59-62.
65. Rothstein JD. 1995. Excitotoxicity and neurodegeneration in amyotrophic lateral sclerosis. Clin Neurosci. 3:348-359.
66. Rothstein JD, Patel S,ReganMR,Haenggeli C,HuangYH, BerglesDE, Jin L, Dykes Hoberg M, Vidensky S, Chung DS, et al. 2005. Betalactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature. 433:73-77.
67. Schuster JE, Fu R, Siddique T, Heckman CJ. 2012. Effect of prolonged riluzole exposure on cultured motoneurons in a mouse model of ALS. J Neurophysiol. 107:484-492.
68. Seal RP, Akil O, Yi E,Weber CM, Grant L, Yoo J, Clause A, Kandler K, Noebels JL, Glowatzki E, et al. 2008. Sensorineural deafness and seizures in mice lacking vesicular glutamate transporter 3. Neuron. 57:263-275.
69. Seijffers R, Zhang J, Matthews JC, Chen A, Tamrazian E, Babaniyi O, Selig M, Hynynen M, Woolf CJ, Brown RH Jr. 2014. ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation. Proc Natl Acad Sci USA. 111:1622-1627.
70. Shepherd GM. 2013. Corticostriatal connectivity and its role in disease. Nat Rev Neurosci. 14:278-291.
71. Shobha K, Vijayalakshmi K, Alladi PA, Nalini A, Sathyaprabha TN, Raju TR. 2007. Altered in-vitro and in-vivo expression of glial glutamate transporter-1 following exposure to cerebrospinal fluid of amyotrophic lateral sclerosis patients. J Neurol Sci. 254:9-16.
72. Spalloni A, Nutini M, Longone P. 2011. Role of the N-methyl-d-aspartate receptors complex in amyotrophic lateral sclerosis. Biochim Biophys Acta. 1832:312-322.
73. Spalloni A, Origlia N, Sgobio C, Trabalza A, Nutini M, Berretta N, Bernardi G, Domenici L, Ammassari-Teule M, Longone P. 2010. Postsynaptic alteration of NR2A subunit and defective autophosphorylation of alphaCaMKII at threonine-286 contribute to abnormal plasticity and morphology of upper motor neurons in presymptomatic SOD1G93A mice, a murine model for amyotrophic lateral sclerosis. Cereb Cortex. 21:796-805.
74. Stuart GJ, Dodt HU, Sakmann B. 1993. Patch-clamp recordings from the soma and dendrites of neurons in brain slices using infrared video microscopy. Pflugers Arch. 423:511-518.
75. Stys PK. 2005. General mechanisms of axonal damage and its prevention. J Neurol Sci. 233:3-13.
76. Suter BA, Migliore M, Shepherd GM. 2013. Intrinsic electrophysiology of mouse corticospinal neurons: A class-specific triad of spike-related properties. Cereb Cortex. 23:1965-1977.
77. Takamori S. 2006. VGLUTs: "exciting" times for glutamatergic research? Neurosci Res. 55:343-351.
78. Thielsen KD, Moser JM, Schmitt-John T, Jensen MS, Jensen K, Holm MM. 2013. The Wobbler Mouse Model of Amyotrophic Lateral Sclerosis (ALS) displays hippocampal hyperexcitability, and reduced number of interneurons, but no presynaptic vesicle release impairments. PLoS One. 8:e82767.
79. Tordera RM, Pei Q, Sharp T. 2005. Evidence for increased expression of the vesicular glutamate transporter, VGLUT1, by a course of antidepressant treatment. J Neurochem. 94: 875-883.
80. Tripodi M, Evers JF, Mauss A, Bate M, Landgraf M. 2008. Structural homeostasis: compensatory adjustments of dendritic arbor geometry in response to variations of synaptic input. PLoS Biol. 6:e260.
81. Uezato A, Meador-Woodruff JH, McCullumsmith RE. 2009. Vesicular glutamate transporter mRNA expression in the medial temporal lobe in major depressive disorder, bipolar disorder, and schizophrenia. Bipolar Disord. 11:711-725.
82. Van Den Bosch L, Van Damme P, Bogaert E, Robberecht W. 2006. The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis. Biochim Biophys Acta. 1762:1068-1082.
83. van Zundert B, Peuscher MH, Hynynen M, Chen A, Neve RL, Brown RH Jr, Constantine-Paton M, BellinghamMC. 2008. Neonatal neuronal circuitry shows hyperexcitable disturbance in a mouse model of the adult-onset neurodegenerative disease amyotrophic lateral sclerosis. J Neurosci. 28:10864-10874.
84. Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, et al. 2009. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science. 323:1208-1211.
85. Vucic S, Cheah BC, Yiannikas C, Kiernan MC. 2011. Cortical excitability distinguishes ALS from mimic disorders. Clin Neurophysiol. 122:1860-1866.
86. Vucic S, Lin CS, Cheah BC, Murray J, Menon P, Krishnan AV, Kiernan MC. 2013. Riluzole exerts central and peripheral modulating effects in amyotrophic lateral sclerosis. Brain. 136:1361-1370.
87. Vucic S, Nicholson GA, Kiernan MC. 2008. Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis. Brain. 131:1540-1550.
88. Vucic S, Ziemann U, Eisen A, Hallett M, Kiernan MC. 2013. Transcranial magnetic stimulation and amyotrophic lateral sclerosis: pathophysiological insights. J Neurol Neurosurg Psychiatry. 84:1161-1170.
89. Wang SJ, Wang KY, Wang WC. 2004. Mechanisms underlying the riluzole inhibition of glutamate release from rat cerebral cortex nerve terminals (synaptosomes). Neuroscience. 125: 191-201.
90. Wijesekera LC, Leigh PN. 2009. Amyotrophic lateral sclerosis. Orphanet J Rare Dis. 4:3.
91. Wilson NR, Kang J, Hueske EV, Leung T, Varoqui H, Murnick JG, Erickson JD, Liu G. 2005. Presynaptic regulation of quantal size by the vesicular glutamate transporter VGLUT1. J Neurosci. 25:6221-6234.
92. Wojcik SM, Rhee JS, Herzog E, Sigler A, Jahn R, Takamori S, Brose N, Rosenmund C. 2004. An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size. Proc Natl Acad Sci USA. 101:7158-7163.
93. Wootz H, Enjin A,Wallen-Mackenzie A, Lindholm D, Kullander K. 2010. Reduced VGLUT2 expression increases motor neuron viability in Sod1(G93A) mice. Neurobiol Dis. 37:58-66.
94. Zilles K. 1985. The Cortex of the Rat. A Stereotaxic Atlas. Berlin: Springer.
95. Zona C, Pieri M, Carunchio I. 2006. Voltage-dependent sodium channels in spinal cord motor neurons display rapid recovery from fast inactivation in a mouse model of amyotrophic lateral sclerosis. J Neurophysiol. 96:3314-3322.