The molecular physiology of the axo-myelinic synapse.


:Myelinated axons efficiently transmit information over long distances. The apposed myelin sheath confers favorable electrical properties, but restricts access of the axon to its extracellular milieu. Therefore, axonal metabolic support may require specific axo-myelinic communication. Here we explored activity-dependent glutamate-mediated signaling from axon to myelin. 2-Photon microscopy was used to image Ca(2+) changes in myelin in response to electrical stimulation of optic nerve axons ex vivo. We show that optic nerve myelin responds to axonal action potentials by a rise in Ca(2+) levels mediated by GluN2D and GluN3A-containing NMDA receptors. Glutamate is released from axons in a vesicular manner that is tetanus toxin-sensitive. The Ca(2+) source for vesicular fusion is provided by ryanodine receptors on axonal Ca(2+) stores, controlled by L-type Ca(2+) channels that sense depolarization of the internodal axolemma. Genetic ablation of GluN2D and GluN3A subunits results in greater lability of the compact myelin. Our results support the existence of a novel synapse between the axon and its myelin, suggesting a means by which traversing action potentials can signal the overlying myelin sheath. This may be an important physiological mechanism by which an axon can signal companion glia for metabolic support or adjust properties of its myelin in a dynamic manner. The axo-myelinic synapse may contribute to learning, while its disturbances may play a role in the pathophysiology of central nervous system disorders such as schizophrenia, where subtle abnormalities of myelinated white matter tracts have been shown in the human, or to frank demyelinating disorders such as multiple sclerosis.


Exp Neurol


Experimental neurology


Micu I,Plemel JR,Lachance C,Proft J,Jansen AJ,Cummins K,van Minnen J,Stys PK




Has Abstract


2016-02-01 00:00:00












  • Allosteric modulation of NMDA receptors alters neurotransmission in the striatum of a mouse model of Parkinson's disease.

    abstract::The GluN2 subunits that compose N-methyl-d-aspartate receptors (NMDARs) are attractive drug targets for therapeutic intervention in several diseases, in particular Parkinson's disease (PD). The precise roles and possible dysfunctions of NMDARs attributed to specific GluN2 subunits are however unresolved. Through the u...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Feng ZJ,Zhang X,Chergui K

    更新日期:2014-05-01 00:00:00

  • Alternative splicing of AMPA receptor subunits in the 6-OHDA-lesioned rat model of Parkinson's disease and L-DOPA-induced dyskinesia.

    abstract::Abnormal corticostriatal plasticity is a key mechanism of L-DOPA-induced dyskinesia (LID) in Parkinson's disease (PD). Antagonists at glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, such as IEM 1460, reduce induction and expression of dyskinesia in rat and non-human primate models ...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Kobylecki C,Crossman AR,Ravenscroft P

    更新日期:2013-09-01 00:00:00

  • Spectral analysis for electroencephalograms: mathematical determination of neurophysiological relationships from records of limited duration.

    abstract::Spectral analysis is a mathematical method which contains and generalizes frequency analysis. The form of spectral analysis most applicable to EEG is tutorially presented, using both algebraic formulae and four simplified illustrative examples. The examples are each converted into an autocorrelogram and auto-spectrogr...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Walter DO

    更新日期:1963-08-01 00:00:00

  • Septations in chronic spinal cord injury cavities contain axons.

    abstract::Human spinal cord injury (SCI) can result in progressive degeneration that may continue for many years and lead to the formation of highly septated cystic cavities. This hallmark feature has been reproduced in experimental models, but neither its pathogenesis nor clinically relevant features have been fully elucidated...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Radojicic M,Reier PJ,Steward O,Keirstead HS

    更新日期:2005-12-01 00:00:00

  • Site specificity of adrenalectomy-induced brain growth.

    abstract::Infant, juvenile, and adult brain growth is modulated by corticosterone. This study was designed to determine whether such modulation is confined to certain specific brain areas, and if the pattern of growth revealed is consistent across strains of rats. Young female Sprague-Dawley-derived rats were either adrenalecto...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Thomas TL,Devenport LD

    更新日期:1988-12-01 00:00:00

  • The effect of GDNF on nigrostriatal dopaminergic function in response to a two-pulse K(+) stimulation.

    abstract::We examined the effect of glial cell line-derived neurotrophic factor (GDNF) upon nigrostriatal dopaminergic function in response to two-pulse potassium (K(+)) stimulation in rats under in vivo microdialysis conditions. The two-pulse infusion protocol permits us to focus upon the role of this neurotrophin as related t...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Xu K,Dluzen DE

    更新日期:2000-12-01 00:00:00

  • 3-Aminobenzamide reduces brain infarction and neutrophil infiltration after transient focal cerebral ischemia in mice.

    abstract::Poly(ADP-ribose) polymerase (PARP) was shown to be detrimental in cerebral ischemia but the mechanisms whereby PARP is deleterious have yet to be determined. They may include a role in neutrophil infiltration known to aggravate ischemic damage. In this context, we investigated the effect of 3-aminobenzamide (3-AB), a ...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Couturier JY,Ding-Zhou L,Croci N,Plotkine M,Margaill I

    更新日期:2003-12-01 00:00:00

  • Synaptic evoked potentials from regenerating dorsal root axons within fetal spinal cord tissue transplants.

    abstract::Previously injured dorsal roots were electrically stimulated to determine if regenerating sensory axons can form physiologically active synaptic contacts with neurons within fetal spinal cord tissue transplants. Dorsal rootlets, sectioned at their spinal cord entry zone, were apposed to intraspinal transplants of feta...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Houle JD,Skinner RD,Garcia-Rill E,Turner KL

    更新日期:1996-06-01 00:00:00

  • Engraftment of embryonic stem cell-derived myogenic progenitors in a dominant model of muscular dystrophy.

    abstract::Muscular dystrophies (MDs) consist of a genetically heterogeneous group of disorders, recessive or dominant, characterized by progressive skeletal muscle weakening. To date, no effective treatment is available. Experimental strategies pursuing muscle regeneration through the transplantation of stem cell preparations h...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Darabi R,Baik J,Clee M,Kyba M,Tupler R,Perlingeiro RC

    更新日期:2009-11-01 00:00:00

  • Impaired axonal transport and altered axolemmal permeability occur in distinct populations of damaged axons following traumatic brain injury.

    abstract::Traumatic axonal injury (TAI) evolves within minutes to hours following traumatic brain injury (TBI). Previous studies have identified axolemmal disruption and impaired axonal transport (AxT) as key mechanisms in the evolution of TAI. While initially hypothesized that axolemmal disruption culminates in impaired AxT, p...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Stone JR,Okonkwo DO,Dialo AO,Rubin DG,Mutlu LK,Povlishock JT,Helm GA

    更新日期:2004-11-01 00:00:00

  • The role of growth factors as a therapeutic approach to demyelinating disease.

    abstract::A variety of growth factors are being explored as therapeutic agents relevant to the axonal and oligodendroglial deficits that occur as a result of demyelinating lesions such as are evident in Multiple Sclerosis (MS). This review focuses on five such proteins that are present in the lesion site and impact oligodendroc...

    journal_title:Experimental neurology

    pub_type: 杂志文章,评审


    authors: Huang Y,Dreyfus CF

    更新日期:2016-09-01 00:00:00

  • Distribution of serotonin 2A and 2C receptor mRNA expression in the cervical ventral horn and phrenic motoneurons following spinal cord hemisection.

    abstract::Cervical spinal cord injury leads to a disruption of bulbospinal innervation from medullary respiratory centers to phrenic motoneurons. Animal models utilizing cervical hemisection result in inhibition of ipsilateral phrenic nerve activity, leading to paralysis of the hemidiaphragm. We have previously demonstrated a r...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Basura GJ,Zhou SY,Walker PD,Goshgarian HG

    更新日期:2001-06-01 00:00:00

  • Effect of systemic kainate administration on cerebral quinolinic acid metabolism in the rat.

    abstract::Systemic administration of kainic acid (12 mg/kg, i.p.), causing the established epileptic syndrome and the associated specific pattern of limbic nerve cell loss, led to substantial time-dependent increases in the brain metabolism of the endogenous excitotoxin, quinolinic acid. These changes preferentially affected bi...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Speciale C,Schwarcz R

    更新日期:1988-01-01 00:00:00

  • Lack of iNOS induction in a severe model of transient focal cerebral ischemia in rats.

    abstract::Calcium-independent nitric oxide synthase (NOS) activity has been reported in ischemic brains and usually attributed to the inducible isoform, iNOS. Because calcium-independent mechanisms have recently been shown to regulate the constitutive calcium-dependent NOS, we proposed to confirm the presence of iNOS activity i...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Lerouet D,Jafarian-Tehrani M,Louin G,Palmier B,Bonnefont-Rousselot D,Plotkine M,Margaill I

    更新日期:2005-09-01 00:00:00

  • The antidepressant sertraline improves the phenotype, promotes neurogenesis and increases BDNF levels in the R6/2 Huntington's disease mouse model.

    abstract::Huntington's disease (HD) is an inherited progressive neurodegenerative disorder characterized by progressive movement, psychiatric and cognitive disturbances. Previous studies have indicated that HD pathogenesis may be mediated in part by loss of brain derived neurotrophic factor (BDNF). Antidepressants selectively b...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Peng Q,Masuda N,Jiang M,Li Q,Zhao M,Ross CA,Duan W

    更新日期:2008-03-01 00:00:00

  • Where attention falls: Increased risk of falls from the converging impact of cortical cholinergic and midbrain dopamine loss on striatal function.

    abstract::Falls are a major source of hospitalization, long-term institutionalization, and death in older adults and patients with Parkinson's disease (PD). Limited attentional resources are a major risk factor for falls. In this review, we specify cognitive-behavioral mechanisms that produce falls and map these mechanisms onto...

    journal_title:Experimental neurology

    pub_type: 杂志文章,评审


    authors: Sarter M,Albin RL,Kucinski A,Lustig C

    更新日期:2014-07-01 00:00:00

  • Parallel development of noradrenergic innervation and cellular compartmentation in the rat spleen.

    abstract::By combining neurochemical measurement of norepinephrine (NE) with double-label immunocytochemistry for tyrosine hydroxylase-positive (TH+) noradrenergic nerves and specific lymphoid markers, we have examined the developmental compartmentation of noradrenergic nerves in the rat spleen. TH+ nerve fibers were present in...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Ackerman KD,Felten SY,Dijkstra CD,Livnat S,Felten DL

    更新日期:1989-03-01 00:00:00

  • Chondroitinase applied to peripheral nerve repair averts retrograde axonal regeneration.

    abstract::Antegrade, target-directed axonal regeneration is the explicit goal of nerve repair. However, aberrant and dysfunctional regrowth is commonly observed as well. At the site of surgical nerve coaptation, axonal sprouts encounter fibrotic connective tissue rich in growth-inhibiting chondroitin sulfate proteoglycan that m...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Graham JB,Neubauer D,Xue QS,Muir D

    更新日期:2007-01-01 00:00:00

  • Pioglitazone activates paraoxonase-2 in the brain: A novel neuroprotective mechanism.

    abstract::Paraoxonase-2 regulates reactive oxygen species production in mitochondria. Stimulating its expression has therapeutic potential for diseases where oxidative stress plays a significant role in the pathology. Evidence suggests that the anti-diabetic drug pioglitazone may provide neuroprotection in Parkinson's disease, ...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Blackburn JK,Curry DW,Thomsen AN,Roth RH,Elsworth JD

    更新日期:2020-05-01 00:00:00

  • Interaction of norepinephrine and superior cervical ganglion input in the rat pineal body.

    abstract::The effects of superior cervical ganglion stimulation and the local application of norepinephrine or its antagonist propranolol were studied in 18 pineal cells. In 61% of the pineal cells, stimulation elicited excitation; the same cells also responded by excitation to norepinephrine ejection. When stimulation and nore...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Reyes-Vazquez C,Dafny N

    更新日期:1985-12-01 00:00:00

  • TREM2 overexpression attenuates neuroinflammation and protects dopaminergic neurons in experimental models of Parkinson's disease.

    abstract::Triggering receptor expressed on myeloid cells-2 (TREM2) was a newly identified receptor expressed on microglia. Several observations support the hypothesis that TREM2 variation may confer susceptibility to Parkinson's disease (PD). Therefore, in this paper, we explored the role of TREM2 in the 1-methyl-4-phenyl-1,2,3...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Ren M,Guo Y,Wei X,Yan S,Qin Y,Zhang X,Jiang F,Lou H

    更新日期:2018-04-01 00:00:00

  • Normalization of NF-κB activity in dorsal root ganglia neurons cultured from diabetic rats reverses neuropathy-linked markers of cellular pathology.

    abstract:AIMS/HYPOTHESIS:Dorsal root ganglia (DRG) sensory neurons cultured from 3 to 5 month streptozotocin (STZ)-induced diabetic rats exhibit structural and biochemical changes seen in peripheral nerve fibers in vivo, including axonal swellings, oxidative damage, reduced axonal sprouting, and decreased NF-κB activity. NF-κB ...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Saleh A,Schapansky J,Smith DR,Young N,Odero GL,Aulston B,Fernyhough P,Glazner GW

    更新日期:2013-03-01 00:00:00

  • Roles of the periaqueductal gray in descending facilitatory and inhibitory controls of intramuscular hypertonic saline induced muscle nociception.

    abstract::Despite the importance of the periaqueductal gray (PAG) in the modulation of nociception and pain, many aspects of the roles of the different columns of the PAG in descending controls: facilitation and inhibition, are not understood. Employing a tonic muscle pain model established by i.m. injection of 5.8% saline into...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Lei J,Sun T,Lumb BM,You HJ

    更新日期:2014-07-01 00:00:00

  • Effects of prolonged retinal ganglion cell inactivity on superior colliculus glucose metabolism in the mature hooded rat.

    abstract::Previous work utilizing the 2-deoxyglucose (2-DG) technique demonstrated that denervation, both direct (enucleation) or indirect (retinal receptor destruction, leaving ganglion cells intact), resulted in a depression followed by an increase in glucose metabolism in the superior colliculus (SC) of the mature hooded rat...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Thurlow GA,Cooper RM

    更新日期:1989-06-01 00:00:00

  • Neural cell adhesion molecule and its polysialic acid moiety exhibit opposing and linked effects on neuropathic hyperalgesia.

    abstract::Spinal lamina II, where nociceptive C-fibers terminate, expresses high amounts of the polysialylated form of neural cell adhesion molecule (PSA-NCAM). While enzymatic removal of the PSA moiety from NCAM did not affect normal sensitivity to thermal stimuli, it exacerbated nerve injury-induced neuropathic hyperalgesia. ...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: El Maarouf A,Kolesnikov Y,Pasternak G,Rutishauser U

    更新日期:2012-02-01 00:00:00

  • Developmental regulation of BDNF and NT-3 expression by quinolinic acid in the striatum and its main connections.

    abstract::Interactions between neurotrophic factors and neurotransmitters participate in the formation and maintenance of appropriate connections, as well as in neurodegenerative processes. Here we have measured changes in the developmental expression pattern of BDNF and NT-3 in the striatum, cortex, and substantia nigra induce...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Checa N,Canals JM,Alberch J

    更新日期:2000-09-01 00:00:00

  • Nerve growth factor receptors in the central nervous system.

    abstract::Nerve growth factor (NGF) is well known to be involved in the development, survival, and maintenance of sympathetic and neural crest-derived sensory neurons in the peripheral nervous system. Over the last 10-15 years, however, the role of NGF as a necessary trophic substrate for magnocellular cholinergic neurons in th...

    journal_title:Experimental neurology

    pub_type: 杂志文章,评审


    authors: Springer JE

    更新日期:1988-12-01 00:00:00

  • Clostridium perfringens prototoxin-induced alteration of endothelial barrier antigen (EBA) immunoreactivity at the blood-brain barrier (BBB).

    abstract::It has been reported that the severe cerebral edema produced in experimental animals by Clostridium perfringens (Cl p) type D epsilon toxin can be prevented by prior treatment with its precursor prototoxin due to competitive binding to endothelial cells (ECs) at the blood-brain barrier (BBB). In this study we investig...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Zhu C,Ghabriel MN,Blumbergs PC,Reilly PL,Manavis J,Youssef J,Hatami S,Finnie JW

    更新日期:2001-05-01 00:00:00

  • Volumetric changes in the anterior olfactory nucleus of the rat after neonatal olfactory deprivation.

    abstract::The effect of olfactory deprivation in the postnatal development of the anterior olfactory nucleus (AON) was studied in 60-day-old rats which underwent unilateral naris closure after birth (postnatal day 1). Volumetric and morphometric analyses of the AON ipsilateral and contralateral to the closed naris were performe...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Barbado MV,Briñón JG,Weruaga E,Porteros A,Arévalo R,Aijón J,Alonso JR

    更新日期:2001-10-01 00:00:00

  • NMDA receptors in the inferior colliculus are critically involved in audiogenic seizures in the adult rats with neonatal hypothyroidism.

    abstract::The effects of N-methyl-d-aspartate (NMDA) and non-NMDA receptor antagonists were compared on audiogenic seizures in the rats neonatally exposed to propylthiouracil (PTU). The rats treated with 0.02% PTU through mother's milk during days 0-19 after delivery showed a high incidence of audiogenic seizures consisting of ...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Higashiyama A,Ishida N,Nishimura T,Yasuda S,Kuroda Y,McEwen BS,Kato N

    更新日期:1998-09-01 00:00:00