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dc.contributor.author
González Inchauspe, Carlota María Fabiola

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Pilati, Nadia
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Di Guilmi, Mariano Nicolás

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Urbano Suarez, Francisco Jose

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Ferrari, Michel D.
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Maagdenberg, Arn M. J. M. van den
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Forsythe, Ian D.
dc.contributor.author
Uchitel, Osvaldo Daniel

dc.date.available
2018-02-28T19:29:25Z
dc.date.issued
2015-01
dc.identifier.citation
González Inchauspe, Carlota María Fabiola; Pilati, Nadia; Di Guilmi, Mariano Nicolás; Urbano Suarez, Francisco Jose; Ferrari, Michel D.; et al.; Familial hemiplegic migraine type-1 mutated cav2.1 calcium channels alter inhibitory and excitatory synaptic transmission in the lateral superior olive of mice; Elsevier Science; Hearing Research; 319; 1-2015; 56-68
dc.identifier.issn
0378-5955
dc.identifier.uri
http://hdl.handle.net/11336/37471
dc.description.abstract
CaV2.1 Ca2+ channels play a key role in triggering neurotransmitter release and mediating synaptic transmission. Familial hemiplegic migraine type-1 (FHM-1) is caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 Ca2+ channels. We used knock-in (KI) transgenic mice harbouring the pathogenic FHM-1 mutation R192Q to study inhibitory and excitatory neurotransmission in the principle neurons of the lateral superior olive (LSO) in the auditory brainstem. We tested if the R192Q FHM-1 mutation differentially affects excitatory and inhibitory synaptic transmission, disturbing the normal balance between excitation and inhibition in this nucleus. Whole cell patch-clamp was used to measure neurotransmitter elicited excitatory (EPSCs) and inhibitory (IPSCs) postsynaptic currents in wild-type (WT) and R192Q KI mice. Our results showed that the FHM-1 mutation in CaV2.1 channels has multiple effects. Evoked EPSC amplitudes were smaller whereas evoked and miniature IPSC amplitudes were larger in R192Q KI compared to WT mice. In addition, in R192Q KI mice, the release probability was enhanced compared to WT, at both inhibitory (0.53±0.02 vs. 0.44±0.01, P=2.10-5, Student's t-test) and excitatory synapses (0.60±0.03 vs. 0.45±0.02, P=4 10-6, Student's t-test). Vesicle pool size was diminished in R192Q KI mice compared to WT mice (68±6 vs 91±7, P=0.008, inhibitory; 104±13 vs 335±30, P=10-6, excitatory, Student's t-test). R192Q KI mice present enhanced short-term plasticity. Repetitive stimulation of the afferent axons caused short-term depression (STD) of E/IPSCs that recovered significantly faster in R192Q KI mice compared to WT. This supports the hypothesis of a gain-of-function of the CaV2.1 channels in R192Q KI mice, which alters the balance of excitatory/inhibitory inputs and could also have implications in the altered cortical excitability responsible for FHM pathology.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science

dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Familial Hemiplegic Migraine Type-1
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Excitatory Postsynaptic Currents (Epsc)
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Inhibitory Postsynaptic Currents (Ipsc)
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Calcium Channels
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Glycine Receptors
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Neurociencias

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Medicina Básica

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CIENCIAS MÉDICAS Y DE LA SALUD

dc.title
Familial hemiplegic migraine type-1 mutated cav2.1 calcium channels alter inhibitory and excitatory synaptic transmission in the lateral superior olive of mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-02-28T14:12:17Z
dc.journal.volume
319
dc.journal.pagination
56-68
dc.journal.pais
Países Bajos

dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: González Inchauspe, Carlota María Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
dc.description.fil
Fil: Pilati, Nadia. University of Leicester; Reino Unido
dc.description.fil
Fil: Di Guilmi, Mariano Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
dc.description.fil
Fil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
dc.description.fil
Fil: Ferrari, Michel D.. Leiden University; Países Bajos
dc.description.fil
Fil: Maagdenberg, Arn M. J. M. van den. Leiden University; Países Bajos
dc.description.fil
Fil: Forsythe, Ian D.. University of Leicester; Reino Unido
dc.description.fil
Fil: Uchitel, Osvaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
dc.journal.title
Hearing Research

dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0378595514001968
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.heares.2014.11.006
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