Hippocampal hyperexcitability underlies enhanced fear memories in TgNTRK3, a/npanic disorder mouse model

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• dc.contributor.author Santos Verdaguer, Mònicaca
• dc.contributor.author D'Amico, Davide, 1983-ca
• dc.contributor.author Spadoni, Omellaca
• dc.contributor.author Amador Arjona, Alejandroca
• dc.contributor.author Stork, Oliverca
• dc.contributor.author Dierssen, Maraca
• dc.date.accessioned 2015-07-09T11:11:03Z
• dc.date.available 2015-07-09T11:11:03Z
• dc.date.issued 2013ca
• dc.description.abstract Panic attacks are a hallmark in panic disorder (PAND). During the panic attack, a strong association with the surrounding context is established suggesting that the hippocampus may be critically involved in the pathophysiology of PAND, given its role in contextual processing. We previously showed that variation in the expression of the neurotrophin tyrosine kinase receptor type 3 (NTRK3) in both PAND patients and a transgenic mouse model (TgNTRK3) may have a role in PAND pathophysiology. Our study examines hippocampal function and activation of the brain fear network in TgNTRK3 mice. TgNTRK3 mice showed increased fear memories accompanied by impaired extinction, congruent with an altered activation pattern of the amygdala-hippocampus-medial prefrontal cortex fear circuit. Moreover, TgNTRK3 mice also showed an unbalanced excitation-to-inhibition ratio in the hippocampal cornu ammonis 3 (CA3)-CA1 subcircuit toward hyperexcitability. The resulting hippocampal hyperexcitability underlies the enhanced fear memories, as supported by the efficacy of tiagabine, a GABA reuptake inhibitor, to rescue fear response. The fearful phenotype appears to be the result of hippocampal hyperexcitability and aberrant fear circuit activation. We conclude that NTRK3 plays a role in PAND by regulating hippocampus-dependent fear memories.
• dc.description.sponsorship The laboratory of M.D. is supported by Departament d'Universitats, Recerca i Societat de la Informació (Grups consolidats 09 2009SGR1313). This work was supported by Grants SAF2010-16427, SAF2007-31093-E, and FIS (PI 082038); Marató TV3; the Jerome Lejeune, Koplowitz, and Areces Foundations; and the European Union (LSHG-CT-2006-037627; CureFXS ERare-EU/FIS PS09102673). The Centro de Investigación Biomédica en Red de Enfermedades Raras is an initiative of the Instituto de Salud Carlos III. M.S. was supported by Fundação para a Ciência e Tecnologica (Portugal) with a postdoctoral fellowship, and D.D. was supported by a La Caixa International PhD Programme fellowship
• dc.format.mimetype application/pdfca
• dc.identifier.citation Santos M, D'Amico D, Spadoni O, Amador-Arjona A, Stork O, Dierssen M./nHippocampal hyperexcitability underlies enhanced fear memories in TgNTRK3, a/npanic disorder mouse model. J Neurosci. 2013 Sep 18; 33(38): 15259-71. DOI:/n10.1523/JNEUROSCI.2161-13.2013ca
• dc.identifier.doi http://dx.doi.org/10.1523/JNEUROSCI.2161-13.2013
• dc.identifier.issn 0270-6474ca
• dc.identifier.uri http://hdl.handle.net/10230/24592
• dc.language.iso engca
• dc.publisher Society for Neuroscienceca
• dc.relation.ispartof Journal of Neuroscience. 2013 Sep 18;33(38):15259-71
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-16427
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2007-31093
• dc.relation.projectID info:eu-repo/grantAgreement/EC/ERC/037627
• dc.rights © Society for Neuroscience http://dx.doi.org/10.1523/JNEUROSCI.2161-13.2013. The work is published under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/
• dc.subject.other Por
• dc.subject.other Hipocamp
• dc.subject.other Memòria -- Fisiologia
• dc.title Hippocampal hyperexcitability underlies enhanced fear memories in TgNTRK3, a/npanic disorder mouse modelca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca