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Reduced cholinergic and glutamatergic synaptic input to regenerated motoneurons after facial nerve repair in rats: potential implications for recovery of motor function

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Abstract

Deafferentation of motoneurons after facial nerve injury is a well-documented phenomenon but whether synaptic inputs to facial motoneurons are completely restored after reinnervation is unknown. Here, we tested the hypothesis that deficits in motor performance after transection/suture of the facial nerve (facial–facial anastomosis, FFA) in adult rats are associated with incomplete recovery of synaptic inputs. At 2 months after FFA, we found, in congruence with previous results, that the amplitude of whisking had recovered to only 31 % of control (sham operation). In the same FFA-treated rats, estimates of number of chemically defined synaptic terminals in the facial nucleus by immunohistochemistry and stereology showed a significant loss, compared with sham controls, of glutamatergic terminals (−26 %) and cholinergic perisomatic boutons (−31 %), but not inhibitory (GABA/glycinergic) terminals (−14 %). Synaptic deficits were accompanied by persistent microgliosis in the facial nucleus but soma area, dendritic arbor volume, and total number of motoneurons were normal. Correlation analyses revealed significant co-variations of whisking amplitude with number of glutamatergic and cholinergic synapses. Compared with 2 months, analyses of animals at 4 months after FFA showed no attenuation of the functional deficit and structural aberrations with one exception, increase of inhibitory terminal numbers beyond control level (+11 %) leading to further reduction of the excitatory/inhibitory terminal ratio. We suggest that deficits in motoneuron innervation in the regenerated facial nucleus—reduced glutamatergic and cholinergic input and reduced excitatory/inhibitory terminal ratio—could attenuate the motor output and, thus, negatively impact the functional performance after facial nerve regeneration.

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References

  • 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 472:257–280. doi:10.1002/cne.20012

    CAS  PubMed  Google Scholar 

  • 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 106:2450–2470. doi:10.1152/jn.01095.2010

    CAS  PubMed Central  PubMed  Google Scholar 

  • Angelov D, Guntinas-Lichius O, Wewetzer K, Neiss W, Streppel M (2005) Axonal branching and recovery of coordinated muscle activity after transection of the facial nerve in adult rats. Adv Anat Embryol Cell Biol 180:1–130

    CAS  PubMed  Google Scholar 

  • Angelov D, Ceynowa M, Guntinas-Lichius O et al (2007) Mechanical stimulation of paralyzed vibrissal muscles following facial nerve injury in adult rat promotes full recovery of whisking. Neurobiol Dis 26:229–242. doi:10.1016/j.nbd.2006.12.016

    PubMed  Google Scholar 

  • Apostolova I, Irintchev A, Schachner M (2006) Tenascin-R restricts posttraumatic remodeling of motoneuron innervation and functional recovery after spinal cord injury in adult mice. J Neurosci 26:7849–7859. doi:10.1523/JNEUROSCI.1526-06.2006

    CAS  PubMed  Google Scholar 

  • Berg A, Zelano J, Stephan A, Thams S, Barres BA, Pekny M, Pekna M, Cullheim S (2012) Reduced removal of synaptic terminals from axotomized spinal motoneurons in the absence of complement C3. Exp Neurol 237:8–17

    PubMed  Google Scholar 

  • Bessis A, Béchade C, Bernard D, Roumier A (2007) Microglial control of neuronal death and synaptic properties. Glia 55:233–238. doi:10.1002/glia.20459

    PubMed  Google Scholar 

  • Bischoff A, Grosheva M, Irintchev A et al (2009) Manual stimulation of the orbicularis oculi muscle improves eyelid closure after facial nerve injury in adult rats. Muscle Nerve 39:197–205. doi:10.1002/mus.21126

    PubMed  Google Scholar 

  • Blinzinger K, Kreutzberg G (1968) Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Z Zellforsch Mikrosk Anat 85:145–157

    CAS  PubMed  Google Scholar 

  • Borke RC, Bridwell RS, Nau ME (1995) The progression of deafferentation as a retrograde reaction to hypoglossal nerve injury. J Neurocytol 24:763–774

    CAS  PubMed  Google Scholar 

  • Bosco A, Steele MR, Vetter ML (2011) Early microglia activation in a mouse model of chronic glaucoma. J Comp Neurol 519:599–620. doi:10.1002/cne.22516

    PubMed  Google Scholar 

  • Brännström T, Kellerth JO (1999) Recovery of synapses in axotomized adult cat spinal motoneurons after reinnervation into muscle. Exp Brain Res 125:19–27

    PubMed  Google Scholar 

  • Brännström T, Havton L, Kellerth JO (1992a) Changes in size and dendritic arborization patterns of adult cat spinal alpha-motoneurons following permanent axotomy. J Comp Neurol 318:439–451

    PubMed  Google Scholar 

  • Brännström T, Havton L, Kellerth JO (1992b) Restorative effects of reinnervation on the size and dendritic arborization patterns of axotomized cat spinal alpha-motoneurons. J Comp Neurol 318:452–461

    PubMed  Google Scholar 

  • Brumovsky P, Watanabe M, Hökfelt 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 147:469–490. doi:10.1016/S0306-4522(07)00254-0

    CAS  PubMed  Google Scholar 

  • Brushart TM, Mesulam MM (1980) Alteration in connections between muscle and anterior horn motoneurons after peripheral nerve repair. Science 208:603–605

    CAS  PubMed  Google Scholar 

  • Bullinger KL, Nardelli P, Pinter MJ, Alvarez FJ, Cope TC (2011) Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. II. Loss of functional connectivity with motoneurons. J Neurophysiol 106:2471–2485. doi:10.1152/jn.01097.2010

    PubMed Central  PubMed  Google Scholar 

  • Bulloch K, Miller MM, Gal-Toth J et al (2008) CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain. J Comp Neurol 508:687–710. doi:10.1002/cne.21668

    PubMed  Google Scholar 

  • Chaudhry FA, Reimer RJ, Bellocchio EE, Danbolt NC, Osen KK, Edwards RH, Storm-Mathisen J (1998) The vesicular GABA transporter, VGAT, localizes to synaptic vesicles in sets of glycinergic as well as GABAergic neurons. J Neurosci 18:9733–9750

    CAS  PubMed  Google Scholar 

  • Chen DH (1978) Qualitative and quantitative study of synaptic displacement in chromatolyzed spinal motoneurons of the cat. J Comp Neurol 177:635–664. doi:10.1002/cne.901770407

    CAS  PubMed  Google Scholar 

  • Chen J, Wu J, Apostolova I, Skup M, Irintchev A, Kugler S, Schachner M (2007) Adeno-associated virus-mediated LI expression promotes functional recovery after spinal cord injury. Brain 130:954–969. doi:10.1093/brain/awm049

    PubMed  Google Scholar 

  • Chen J, Lee HJ, Jakovcevski I et al (2010) The extracellular matrix glycoprotein tenascin-C is beneficial for spinal cord regeneration. Mol Ther 18:1769–1777. doi:10.1038/mt.2010.133

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cocchia D (1981) Immunocytochemical localization of S-100 protein in the brain of adult rat. An ultrastructural study. Cell Tissue Res 214:529–540

    CAS  PubMed  Google Scholar 

  • Cossu G, Valls-Solé J, Valldeoriola F, Muñoz E, Benítez P, Aguilar F (1999) Reflex excitability of facial motoneurons at onset of muscle reinnervation after facial nerve palsy. Muscle Nerve 22:614–620

    CAS  PubMed  Google Scholar 

  • Cullheim S, Thams S (2007) The microglial networks of the brain and their role in neuronal network plasticity after lesion. Brain Res Rev 55:89–96

    CAS  PubMed  Google Scholar 

  • Davidoff M, Irintchev A (1986) Acetylcholinesterase activity and type C synapses in the hypoglossal, facial and spinal-cord motor nuclei of rats: an electron-microscope study. Histochemistry 84:515–524

    CAS  PubMed  Google Scholar 

  • Delgado-Garcia JM, Del Pozo F, Spencer RF, Baker R (1988) Behavior of neurons in the abducens nucleus of the alert cat-III. Axotomized motoneurons. Neuroscience 24:143–160. doi:10.1016/0306-4522(88)90319-3

    CAS  PubMed  Google Scholar 

  • Eleore L, Vassias I, Vidal PP, de Waele C (2005a) Modulation of the glutamatergic receptors (AMPA and NMDA) and of glutamate vesicular transporter 2 in the rat facial nucleus after axotomy. Neuroscience 136:147–160. pii:S0306-4522(05)00688-3

    CAS  PubMed  Google Scholar 

  • Eleore L, Vassias I, Vidal PP, Triller A, de Waele C (2005b) Modulation of glycine receptor subunits and gephyrin expression in the rat facial nucleus after axotomy. Eur J Neurosci 21:669–678. pii:EJN3887

    PubMed  Google Scholar 

  • Foehring RC, Sypert GW, Munson JB (1986) Properties of self-reinnervated motor units of medial gastrocnemius of cat I. Long-term reinnervation. J Neurophysiol 55:931–946

    CAS  PubMed  Google Scholar 

  • Fortune T, Lurie DI (2009) Chronic low-level lead exposure affects the monoaminergic system in the mouse superior olivary complex. J Comp Neurol 513:542–558. doi:10.1002/cne.21978

    CAS  PubMed Central  PubMed  Google Scholar 

  • Franchi G (2000) Changes in motor representation related to facial nerve damage and regeneration in adult rats. Exp Brain Res 135:53–65

    CAS  PubMed  Google Scholar 

  • Friauf E (1986) Morphology of motoneurons in different subdivisions of the rat facial nucleus stained intracellularly with horseradish peroxidase. J Comp Neurol 253:231–241

    CAS  PubMed  Google Scholar 

  • Fu S, Gordon T (1997) The cellular and molecular basis of peripheral nerve regeneration. Mol Neurobiol 14:67–116

    CAS  PubMed  Google Scholar 

  • Furutani R, Izawa T, Sugita S (2004) Distribution of facial motoneurons innervating the common facial muscles of the rabbit and rat. Okajimas Folia Anat Jpn 81:101–108

    PubMed  Google Scholar 

  • Galtrey CM, Asher RA, Nothias F, Fawcett JW (2007) Promoting plasticity in the spinal cord with chondroitinase improves functional recovery after peripheral nerve repair. Brain 130:926–939. doi:10.1093/brain/awl372

    PubMed  Google Scholar 

  • Ge SN, Ma YF, Hioki H et al (2010) Coexpression of VGLUT1 and VGLUT2 in trigeminothalamic projection neurons in the principal sensory trigeminal nucleus of the rat. J Comp Neurol 518:3149–3168. doi:10.1002/cne.22389

    CAS  PubMed  Google Scholar 

  • Ghandour MS, Langley OK, Labourdette G, Vincendon G, Gombos G (1981) Specific and artefactual cellular localizations of S 100 protein: an astrocyte marker in rat cerebellum. Dev Neurosci 4:66–78

    CAS  PubMed  Google Scholar 

  • Graeber MB (2010) Changing face of microglia. Science 330:783–788. pii:330/6005/783

    CAS  PubMed  Google Scholar 

  • Graeber MB, Kreutzberg GW (1988) Delayed astrocyte reaction following facial nerve axotomy. J Neurocytol 17:209–220

    CAS  PubMed  Google Scholar 

  • Graeber MB, Streit WJ (2010) Microglia: biology and pathology. Acta Neuropathol 119:89–105. doi:10.1007/s00401-009-0622-0

    PubMed  Google Scholar 

  • Graeber MB, Tetzlaff W, Streit WJ, Kreutzberg GW (1988) Microglial cells but not astrocytes undergo mitosis following rat facial nerve axotomy. Neurosci Lett 85:317–321

    CAS  PubMed  Google Scholar 

  • Graeber MB, Bise K, Mehraein P (1993) Synaptic stripping in the human facial nucleus. Acta Neuropathol 86:179–181

    CAS  PubMed  Google Scholar 

  • Graeber MB, López-Redondo F, Ikoma E et al (1998) The microglia/macrophage response in the neonatal rat facial nucleus following axotomy. Brain Res 813:241–253. doi:10.1016/S0006-8993(98)00859-2

    CAS  PubMed  Google Scholar 

  • Gras C, Vinatier J, Amilhon B et al (2005) Developmentally regulated expression of VGLUT3 during early post-natal life. Neuropharmacology 49:901–911. doi:10.1016/S0028-3908(05)00286-8

    CAS  PubMed  Google Scholar 

  • Guntinas-Lichius O, Neiss W, Gunkel A, Stennert E (1994) Differences in glial, synaptic and motoneuron responses in the facial nucleus of the rat brainstem following facial nerve resection and nerve suture reanastomosis. Eur Arch Otorhinolaryngol 251:410–417

    CAS  PubMed  Google Scholar 

  • Guntinas-Lichius O, Martinez-Portillo F, Lebek J, Angelov DN, Stennert E, Neiss WF (1997) Nimodipine maintains in vivo the increase in GFAP and enhances the astroglial ensheathment of surviving motoneurons in the rat following permanent target deprivation. J Neurocytol 26:241–248

    CAS  PubMed  Google Scholar 

  • Guntinas-Lichius O, Angelov D, Morellini F, Lenzen M, Skouras E, Schachner M, Irintchev A (2005a) Opposite impacts of tenascin-C and tenascin-R deficiency in mice on the functional outcome of facial nerve repair. Eur J Neurosci 22:2171–2179. doi:10.1111/j.1460-9568.2005.04424.x

    PubMed  Google Scholar 

  • Guntinas-Lichius O, Irintchev A, Streppel M et al (2005b) Factors limiting motor recovery after facial nerve transection in the rat: combined structural and functional analyses. Eur J Neurosci 21:391–402. doi:10.1111/j.1460-9568.2005.03877.x

    PubMed  Google Scholar 

  • Guntinas-Lichius O, Hundeshagen G, Paling T, Angelov D (2007a) Impact of different types of facial nerve reconstruction on the recovery of motor function: an experimental study in adult rats. Neurosurgery 61:1276–1283

    PubMed  Google Scholar 

  • Guntinas-Lichius O, Straesser A, Streppel M (2007b) Quality of life after facial nerve repair. Laryngoscope 117:421–426. pii:00005537-200703000-00006

    PubMed  Google Scholar 

  • Guntinas-Lichius O, Glowka TR, Angelov DN, Irintchev A, Neiss WF (2011) Improved functional recovery after facial nerve reconstruction by temporary denervation of the contralateral mimic musculature with botulinum toxin in rats. Neurorehabilitation Neural Repair 25:15–23. doi:10.1177/1545968310376058

    PubMed  Google Scholar 

  • Guseva D, Angelov D, Irintchev A, Schachner M (2009) Ablation of adhesion molecule L1 in mice favours Schwann cell proliferation and functional recovery after peripheral nerve injury. Brain 132:2180–2195. doi:10.1093/brain/awp160

    PubMed  Google Scholar 

  • Guseva D, Zerwas M, Xiao MF, Jakovcevski I, Irintchev A, Schachner M (2011) Adhesion molecule L1 overexpressed under the control of the neuronal Thy-1 promoter improves myelination after peripheral nerve injury in adult mice. Exp Neurol 229:339–352. doi:10.1016/j.expneurol.2011.02.018

    CAS  PubMed  Google Scholar 

  • Hadlock TA, Kowaleski J, Lo D, Mackinnon SE, Heaton JT (2010) Rodent facial nerve recovery after selected lesions and repair techniques. Plast Reconstr Surg 125:99–109. pii:00006534-201001000-00013

    CAS  PubMed  Google Scholar 

  • Haftel V, Bichler E, Wang Q, Prather J, Pinter M, Cope T (2005) Central suppression of regenerated proprioceptive afferents. J Neurosci 25:4733–4742. doi:10.1523/JNEUROSCI.4895-04.2005

    CAS  PubMed  Google Scholar 

  • Hattox A, Li Y, Keller A (2003) Serotonin regulates rhythmic whisking. Neuron 39:343–352. pii:S089662730300391X

    CAS  PubMed  Google Scholar 

  • Heckman CJ, Hyngstrom AS, Johnson MD (2008) Active properties of motoneurone dendrites: diffuse descending neuromodulation, focused local inhibition. J Physiol 586:1225–1231. doi:10.1113/jphysiol.2007.145078

    CAS  PubMed Central  PubMed  Google Scholar 

  • Heckroth JA (1994a) A quantitative morphological analysis of the cerebellar nuclei in normal and lurcher mutant mice. II. Volumetric changes in cytological components. J Comp Neurol 343:183–192. doi:10.1002/cne.903430114

    CAS  PubMed  Google Scholar 

  • Heckroth JA (1994b) Quantitative morphological analysis of the cerebellar nuclei in normal and lurcher mutant mice. I. Morphology and cell number. J Comp Neurol 343:173–182. doi:10.1002/cne.903430113

    CAS  PubMed  Google Scholar 

  • Hellström J, Oliveira AL, Meister B, Cullheim S (2003) Large cholinergic nerve terminals on subsets of motoneurons and their relation to muscarinic receptor type 2. J Comp Neurol 460:476–486. doi:10.1002/cne.10648

    PubMed  Google Scholar 

  • Herzog E, Gilchrist J, Gras C et al (2004) Localization of VGLUT3, the vesicular glutamate transporter type 3, in the rat brain. Neuroscience 123:983–1002. pii:S0306452203008479

    CAS  PubMed  Google Scholar 

  • Hildebrand C, Kocsis JD, Berglund S, Waxman SG (1985) Myelin sheath remodelling in regenerated rat sciatic nerve. Brain Res 358:163–170. doi:10.1016/0006-8993(85)90960-6

    CAS  PubMed  Google Scholar 

  • Hoover DB, Hancock JC (1985) Effect of facial nerve transection on acetylcholinesterase, choline acetyltransferase and [3H]quinuclidinyl benzilate binding in rat facial nuclei. Neuroscience 15:481–487

    CAS  PubMed  Google Scholar 

  • Hsu DT, Price JL (2009) Paraventricular thalamic nucleus: subcortical connections and innervation by serotonin, orexin, and corticotropin-releasing hormone in macaque monkeys. J Comp Neurol 512:825–848. doi:10.1002/cne.21934

    PubMed Central  PubMed  Google Scholar 

  • Ijkema-Paassen J, Meek MF, Gramsbergen A (2002) Reinnervation of muscles after transection of the sciatic nerve in adult rats. Muscle Nerve 25:891–897. doi:10.1002/mus.10130

    PubMed  Google Scholar 

  • Imai Y, Ibata I, Ito D, Ohsawa K, Kohsaka S (1996) A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem Biophys Res Commun 224:855–862. pii:S0006-291X(96)91112-2

    CAS  PubMed  Google Scholar 

  • Irintchev A (2011) Potentials and limitations of peripheral nerve injury models in rodents with particular reference to the femoral nerve. Ann Anat 194:276–285. doi:10.1016/j.aanat.2011.02.019

    Google Scholar 

  • Irintchev A, Rollenhagen A, Troncoso E, Kiss J, Schachner M (2005) Structural and functional aberrations in the cerebral cortex of tenascin-C deficient mice. Cereb Cortex 15:950–962. doi:10.1093/cercor/bhh195

    PubMed  Google Scholar 

  • Issa AN, Zhan WZ, Sieck GC, Mantilla CB (2010) Neuregulin-1 at synapses on phrenic motoneurons. J Comp Neurol 518:4213–4225. doi:10.1002/cne.22449

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ito D, Imai Y, Ohsawa K, Nakajima K, Fukuuchi Y, Kohsaka S (1998) Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res Mol Brain Res 57:1–9. pii:S0169328X98000400

    CAS  PubMed  Google Scholar 

  • Jakovcevski I, Wu J, Karl N et al (2007) Glial scar expression of CHL1, the close homolog of the adhesion molecule L1, limits recovery after spinal cord injury. J Neurosci 27:7222–7233. doi:10.1523/JNEUROSCI.0739-07.2007

    CAS  PubMed  Google Scholar 

  • Jakovcevski I, Siering J, Hargus G et al (2009) Close homologue of adhesion molecule L1 promotes survival of Purkinje and granule cells and granule cell migration during murine cerebellar development. J Comp Neurol 513:496–510. doi:10.1002/cne.21981

    PubMed  Google Scholar 

  • Jinno S, Yamada J (2012) Using comparative anatomy in the axotomy model to identify distinct roles for microglia and astrocytes in synaptic stripping. Neuron Glia Biol 1–12. doi:10.1017/S1740925X11000135

  • Kaneko T, Fujiyama F, Hioki H (2002) Immunohistochemical localization of candidates for vesicular glutamate transporters in the rat brain. J Comp Neurol 444:39–62. doi:10.1002/cne.10129

    CAS  PubMed  Google Scholar 

  • Kerns JM, Hinsman EJ (1973a) Neuroglial response to sciatic neurectomy. I. Light microscopy and autoradiography. J Comp Neurol 151:237–254. doi:10.1002/cne.901510303

    CAS  PubMed  Google Scholar 

  • Kerns JM, Hinsman EJ (1973b) Neuroglial response to sciatic neurectomy II. Electron microscopy. J Comp Neurol 151:255–280. doi:10.1002/cne.901510304

    CAS  PubMed  Google Scholar 

  • Kim JE, Liu BP, Park JH, Strittmatter SM (2004) Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury. Neuron 44:439–451. pii:S0896627304006737

    CAS  PubMed  Google Scholar 

  • Kitzman P (2007) VGLUT1 and GLYT2 labeling of sacrocaudal motoneurons in the spinal cord injured spastic rat. Exp Neurol 204:195–204. pii:S0014-4886(06)00593-0

    CAS  PubMed  Google Scholar 

  • Kocsis JD, Waxman SG (1983) Long-term regenerated nerve fibres retain sensitivity to potassium channel blocking agents. Nature 304:640–642

    CAS  PubMed  Google Scholar 

  • Kou SY, Chiu AY, Patterson PH (1995) Differential regulation of motor neuron survival and choline acetyltransferase expression following axotomy. J Neurobiol 27:561–572. doi:10.1002/neu.480270410

    CAS  PubMed  Google Scholar 

  • Kreutzberg GW (1993) Dynamic changes in motoneurons during regeneration. Restor Neurol Neurosci 5:59–60. pii:P1N0393420065729

    CAS  PubMed  Google Scholar 

  • Kwok JC, Dick G, Wang D, Fawcett JW (2011) Extracellular matrix and perineuronal nets in CNS repair. Dev Neurobiol 71:1073–1089

    CAS  PubMed  Google Scholar 

  • Laskawi R, Wolff JR (1996) Changes in glial fibrillary acidic protein immunoreactivity in the rat facial nucleus following various types of nerve lesions. Eur Arch Otorhinolaryngol 253:475–480

    CAS  PubMed  Google Scholar 

  • LeDoux MS, Lorden JF, Smith JM, Mays LE (1998) Serotonergic modulation of eye blinks in cat and monkey. Neurosci Lett 253:61–64. doi:10.1016/S0304-3940(98)00616-8

    CAS  PubMed  Google Scholar 

  • Lee S, Wolfe S (2000) Peripheral nerve injury and repair. J Am Acad Orthop Surg 8:243–252

    CAS  PubMed  Google Scholar 

  • Lee HJ, Jakovcevski I, Radonjic N, Hoelters L, Schachner M, Irintchev A (2009) Better functional outcome of compression spinal cord injury in mice is associated with enhanced H-reflex responses. Exp Neurol 216:365–374. doi:10.1016/j.expneurol.2008.12.009

    PubMed  Google Scholar 

  • Lee HJ, Bian S, Jakovcevski I, Wu B, Irintchev A, Schachner M (2012) Delayed applications of L1 and chondroitinase ABC promote recovery after spinal cord injury. J Neurotrauma 29:1850–1863. doi:10.1089/neu.2011.2290

    Google Scholar 

  • Lindå H, Shupliakov O, Ornung G, Ottersen OP, Storm-Mathisen J, Risling M, Cullheim S (2000) Ultrastructural evidence for a preferential elimination of glutamate-immunoreactive synaptic terminals from spinal motoneurons after intramedullary axotomy. J Comp Neurol 425:10–23. doi:10.1002/1096-9861(20000911)425

    PubMed  Google Scholar 

  • Ludwin SK, Kosek JC, Eng LF (1976) The topographical distribution of S-100 and GFA proteins in the adult rat brain: an immunohistochemical study using horseradish peroxidase-labelled antibodies. J Comp Neurol 165:197–207. doi:10.1002/cne.901650206

    CAS  PubMed  Google Scholar 

  • Lundborg G (2003) Richard P. Bunge memorial lecture. Nerve injury and repair–a challenge to the plastic brain. J Peripher Nerv Syst 8:209–226

    PubMed  Google Scholar 

  • Lundborg G, Rosén B (2007) Hand function after nerve repair. Acta Physiol (Oxf) 189:207–217. pii:APS1653

    CAS  Google Scholar 

  • Lux HD, Winter P (1968) Studies on EPSPs in normal and retrograde reacting facial motoneurons. Proceedings of International Union Physiological Science 7, abstr. 818

  • Madison RD, Sofroniew MV, Robinson GA (2009) Schwann cell influence on motor neuron regeneration accuracy. Neuroscience 163:213–221. doi:10.1016/j.neuroscience.2009.05.073

    CAS  PubMed Central  PubMed  Google Scholar 

  • Marino P, Norreel JC, Schachner M, Rougon G, Amoureux MC (2009) A polysialic acid mimetic peptide promotes functional recovery in a mouse model of spinal cord injury. Exp Neurol 219:163–174. doi:10.1016/S0014-4886(09)00190-3

    CAS  PubMed  Google Scholar 

  • Matsuura J, Ajiki K, Ichikawa T, Misawa H (1997) Changes of expression levels of choline acetyltransferase and vesicular acetylcholine transporter mRNAs after transection of the hypoglossal nerve in adult rats. Neurosci Lett 236:95–98. doi:10.1016/S0304-3940(97)00763-5

    CAS  PubMed  Google Scholar 

  • McIntire SL, Reimer RJ, Schuske K, Edwards RH, Jorgensen EM (1997) Identification and characterization of the vesicular GABA transporter. Nature 389:870–876. doi:10.1038/39908

    CAS  PubMed  Google Scholar 

  • Mehanna A, Mishra B, Kurschat N et al (2009) Polysialic acid glycomimetics promote myelination and functional recovery after peripheral nerve injury in mice. Brain 132:1449–1462. doi:10.1093/brain/awp128

    PubMed  Google Scholar 

  • Mert T, Gunay I, Daglioglu YK (2004) Role of potassium channels in the frequency-dependent activity of regenerating nerves. Pharmacology 72:157–166. pii:PHA2004072003157

    CAS  PubMed  Google Scholar 

  • Miles GB, Hartley R, Todd AJ, Brownstone RM (2007) Spinal cholinergic interneurons regulate the excitability of motoneurons during locomotion. Proc Natl Acad Sci USA 104:2448–2453. doi:10.1073/pnas.0611134104

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moran LB, Graeber MB (2004) The facial nerve axotomy model. Brain Res Brain Res Rev 44:154–178. pii:S0165017303002595

    PubMed  Google Scholar 

  • Moreno N, Morona R, López JM, González A (2010) Subdivisions of the turtle Pseudemys scripta subpallium based on the expression of regulatory genes and neuronal markers. J Comp Neurol 518:4877–4902. doi:10.1002/cne.22493

    PubMed  Google Scholar 

  • Nacimiento W, Podoll K, Graeber MB et al (1992) Contralateral early blink reflex in patients with facial nerve palsy: indication for synaptic reorganization in the facial nucleus during regeneration. J Neurol Sci 109:148–155. doi:10.1016/0022-510X(92)90161-D

    CAS  PubMed  Google Scholar 

  • Nagy JI, Yamamoto T, Jordan LM (1993) Evidence for the cholinergic nature of C-terminals associated with subsurface cisterns in alpha-motoneurons of rat. Synapse 15:17–32. doi:10.1002/syn.890150103

    CAS  PubMed  Google Scholar 

  • Navarro X, Vivó M, Valero-Cabré A (2007) Neural plasticity after peripheral nerve injury and regeneration. Prog Neurobiol 82:163–201. pii:S0301-0082(07)00109-8

    CAS  PubMed  Google Scholar 

  • Newcomb JM, Fickbohm DJ, Katz PS (2006) Comparative mapping of serotonin-immunoreactive neurons in the central nervous systems of nudibranch molluscs. J Comp Neurol 499:485–505. doi:10.1002/cne.21111

    PubMed  Google Scholar 

  • Nickerson Poulin A, Guerci A, El Mestikawy S, Semba K (2006) Vesicular glutamate transporter 3 immunoreactivity is present in cholinergic basal forebrain neurons projecting to the basolateral amygdala in rat. J Comp Neurol 498:690–711. doi:10.1002/cne.21081

    PubMed  Google Scholar 

  • Nishimura Y, Asahara T, Yamamoto T, Tanaka T (1992) Observations on morphology and electrophysiological properties of the normal and axotomized facial motoneurons in the cat. Brain Res 596:305–310. doi:10.1016/0006-8993(92)91562-S

    CAS  PubMed  Google Scholar 

  • Ogata K, Kosaka T (2002) Structural and quantitative analysis of astrocytes in the mouse hippocampus. Neuroscience 113:221–233. pii:S0306452202000416

    CAS  PubMed  Google Scholar 

  • Oliveira AL, Hydling F, Olsson E et al (2003) Cellular localization of three vesicular glutamate transporter mRNAs and proteins in rat spinal cord and dorsal root ganglia. Synapse 50:117–129. doi:10.1002/syn.10249

    CAS  PubMed  Google Scholar 

  • Oliveira AL, Thams S, Lidman O, Piehl F, Hökfelt T, Kärre K, Lindå H, Cullheim S (2004) A role for MHC class I molecules in synaptic plasticity and regeneration of neurons after axotomy. Proc Natl Acad Sci USA 101:17843–17848

    CAS  PubMed Central  PubMed  Google Scholar 

  • Perez-Torrero E, Torrero C, Salas M (2001) Effects of perinatal undernourishment on neuronal development of the facial motor nucleus in the rat. Brain Res 905:54–62

    CAS  PubMed  Google Scholar 

  • Rasmussen K, Aghajanian GK (1990) Serotonin excitation of facial motoneurons: receptor subtype characterization. Synapse 5:324–332. doi:10.1002/syn.890050409

    CAS  PubMed  Google Scholar 

  • Robinson L (2000) Traumatic injury to peripheral nerves. Muscle Nerve 23:863–873

    CAS  PubMed  Google Scholar 

  • Sanes JN, Suner S, Donoghue JP (1990) Dynamic organization of primary motor cortex output to target muscles in adult rats. I. Long-term patterns of reorganization following motor or mixed peripheral nerve lesions. Exp Brain Res 79:479–491

    CAS  PubMed  Google Scholar 

  • Schäfer MK, Varoqui H, Defamie N, Weihe E, Erickson JD (2002) Molecular cloning and functional identification of mouse vesicular glutamate transporter 3 and its expression in subsets of novel excitatory neurons. J Biol Chem 277:50734–50748. doi:http://www.jbc.org/content/early/2002/10/15/jbc.M206738200

    PubMed  Google Scholar 

  • Schmidt BJ, Jordan LM (2000) The role of serotonin in reflex modulation and locomotor rhythm production in the mammalian spinal cord. Brain Res Bull 53:689–710. doi:10.1016/S0361-9230(00)00402-0

    CAS  PubMed  Google Scholar 

  • Scholz T, Krichevsky A, Sumarto A, Jaffurs D, Wirth GA, Paydar K, Evans GR (2009) Peripheral nerve injuries: an international survey of current treatments and future perspectives. J Reconstr Microsurg 25:339–344. doi:10.1055/s-0029-1215529

    PubMed  Google Scholar 

  • Sherwood CC (2005) Comparative anatomy of the facial motor nucleus in mammals, with an analysis of neuron numbers in primates. Anat Rec A Discov Mol Cell Evol Biol 287:1067–1079. doi:10.1002/ar.a.20259

    PubMed  Google Scholar 

  • Shi H, Cui H, Alam G et al (2008) Nestin expression defines both glial and neuronal progenitors in postnatal sympathetic ganglia. J Comp Neurol 508:867–878. doi:10.1002/cne.21719

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sofroniew MV, Schrell U (1982) Long-term storage and regular repeated use of diluted antisera in glass staining jars for increased sensitivity, reproducibility, and convenience of single- and two-color light microscopic immunocytochemistry. J Histochem Cytochem 30:504–511

    CAS  PubMed  Google Scholar 

  • Søreide AJ (1981) Variations in the perineuronal glial changes after different types of nerve lesion: light and electron microscopic investigations on the facial nucleus of the rat. Neuropathol Appl Neurobiol 7:195–204

    PubMed  Google Scholar 

  • Sumner BE (1975) A quantitative analysis of boutons with different types of synapse in normal and injured hypoglossal nuclei. Exp Neurol 49:406–417. doi:10.1016/0014-4886(75)90097-7

    CAS  PubMed  Google Scholar 

  • Sumner A (1990) Aberrant reinnervation. Muscle Nerve 13:801–803

    CAS  PubMed  Google Scholar 

  • Sumner BE, Sutherland FI (1973) Quantitative electron microscopy on the injured hypoglossal nucleus in the rat. J Neurocytol 2:315–328

    CAS  PubMed  Google Scholar 

  • Sumner BE, Watson WE (1971) Retraction and expansion of the dendritic tree of motor neurones of adult rats induced in vivo. Nature 233:273–275

    CAS  PubMed  Google Scholar 

  • Svensson M, Aldskogius H (1992) The effect of axon injury on microtubule-associated protein MAP2 mRNA in the hypoglossal nucleus of the adult rat. Brain Res 581:319–322

    CAS  PubMed  Google Scholar 

  • Tatetsu M, Kim J, Kina S, Sunakawa H, Takayama C (2012) GABA/glycine signaling during degeneration and regeneration of mouse hypoglossal nerves. Brain Res 1446:22–33. doi:10.1016/j.brainres.2012.01.048

    CAS  PubMed  Google Scholar 

  • Taylor KS, Anastakis DJ, Davis KD (2009) Cutting your nerve changes your brain. Brain 132:3122–3133. pii:awp231

    PubMed  Google Scholar 

  • Tereshchenko Y, Morellini F, Dityatev A, Schachner M, Irintchev A (2011) Neural cell adhesion molecule ablation in mice causes hippocampal dysplasia and loss of septal cholinergic neurons. J Comp Neurol 519:2475–2492. doi:10.1002/cne.22636

    CAS  PubMed  Google Scholar 

  • Thams S, Oliveira A, Cullheim S (2008) MHC class I expression and synaptic plasticity after nerve lesion. Brain Res Rev 57:265–269

    CAS  PubMed  Google Scholar 

  • Todd AJ, Hughes DI, Polgár 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 17:13–27. pii:2406

    CAS  PubMed  Google Scholar 

  • Tomov T, Guntinas-Lichius O, Grosheva M, Streppel M, Schraermeyer U, Neiss W, Angelov D (2002) An example of neural plasticity evoked by putative behavioral demand and early use of vibrissal hairs after facial nerve transection. Exp Neurol 178:207–218

    PubMed  Google Scholar 

  • Ulrich-Lai YM, Jones KR, Ziegler DR, Cullinan WE, Herman JP (2011) Forebrain origins of glutamatergic innervation to the rat paraventricular nucleus of the hypothalamus: differential inputs to the anterior versus posterior subregions. J Comp Neurol 519:1301–1319. doi:10.1002/cne.22571

    CAS  PubMed Central  PubMed  Google Scholar 

  • Valls-Solé J, Montero J (2003) Movement disorders in patients with peripheral facial palsy. Mov Disord 18:1424–1435. doi:10.1002/mds.10605

    PubMed  Google Scholar 

  • Valls-Sole J, Castillo CD, Casanova-Molla J, Costa J (2010) Clinical consequences of reinnervation disorders after focal peripheral nerve lesions. Clin Neurophysiol. doi:10.1016/S1388-2457(10)00549-3

    Google Scholar 

  • Vanderhaeghen P, Cheng HJ (2010) Guidance molecules in axon pruning and cell death. Cold Spring Harb Perspect Biol 2:a001859. doi:10.1101/cshperspect.a001859

    PubMed Central  PubMed  Google Scholar 

  • VanderMaelen CP, Aghajanian GK (1980) Intracellular studies showing modulation of facial motoneuron excitability by serotonin. Nature 287:346–347

    CAS  PubMed  Google Scholar 

  • Vaughan DW (1994) Effects of peripheral axotomy on presynaptic axon terminals with GABA-like immunoreactivity. Anat Rec 238:248–262. doi:10.1002/ar.1092380211

    CAS  PubMed  Google Scholar 

  • Wall JT, Kaas JH, Sur M, Nelson RJ, Felleman DJ, Merzenich MM (1986) Functional reorganization in somatosensory cortical areas 3b and 1 of adult monkeys after median nerve repair: possible relationships to sensory recovery in humans. J Neurosci 6:218–233

    CAS  PubMed  Google Scholar 

  • Wilson JM, Rempel J, Brownstone RM (2004) Postnatal development of cholinergic synapses on mouse spinal motoneurons. J Comp Neurol 474:13–23. doi:10.1002/cne.20089

    CAS  PubMed  Google Scholar 

  • Wojcik SM, Katsurabayashi S, Guillemin I, Friauf E, Rosenmund C, Brose N, Rhee JS (2006) A shared vesicular carrier allows synaptic corelease of GABA and glycine. Neuron 50:575–587. doi:10.1016/S0896-6273(06)00307-2

    CAS  PubMed  Google Scholar 

  • Zagoraiou L, Akay T, Martin JF, Brownstone RM, Jessell TM, Miles GB (2009) A cluster of cholinergic premotor interneurons modulates mouse locomotor activity. Neuron 64:645–662. doi:10.1016/j.neuron.2009.10.017

    CAS  PubMed Central  PubMed  Google Scholar 

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  1. Abdulrahman Raslan

    Present address: Fachrichtung 2.1 Anatomie und Zellbiologie, Medizinische Fakultät der Universität des Saarlandes, Kirrberger Str. 1, Geb. 61, 66421, Homburg/Saar, Germany

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  1. Department of Otorhinolaryngology, University Hospital Jena, Lessingstrasse 2, 07740, Jena, Germany

    Abdulrahman Raslan, Philipp Ernst, Marlen Werle, Heike Thieme, Katja Szameit, Mira Finkensieper, Orlando Guntinas-Lichius & Andrey Irintchev

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Abdulrahman Raslan and Philipp Ernst contributed equally to this work.

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Raslan, A., Ernst, P., Werle, M. et al. Reduced cholinergic and glutamatergic synaptic input to regenerated motoneurons after facial nerve repair in rats: potential implications for recovery of motor function. Brain Struct Funct 219, 891–909 (2014). https://doi.org/10.1007/s00429-013-0542-6

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