67 research outputs found
The Geisler Method: Tracing Activity-Dependent cGMP Plasticity Changes upon Double Detection of mRNA and Protein on Brain Slices
No full textNoise-induced inner hair cell ribbon loss disturbs central arc mobilization: a novel molecular paradigm for understanding tinnitus
No full textet al.Increasing evidence shows that hearing loss is a risk factor for tinnitus and hyperacusis. Although both often coincide, a causal relationship between tinnitus and hyperacusis has not been shown. Currently, tinnitus and hyperacusis are assumed to be caused by elevated responsiveness in subcortical circuits. We examined both the impact of different degrees of cochlear damage and the influence of stress priming on tinnitus induction. We used (1) a behavioral animal model for tinnitus designed to minimize stress, (2) ribbon synapses in inner hair cells (IHCs) as a measure for deafferentation, (3) the integrity of auditory brainstem responses (ABR) to detect differences in stimulus-evoked neuronal activity, (4) the expression of the activity-regulated cytoskeletal protein, Arc, to identify long-lasting changes in network activity within the basolateral amygdala (BLA), hippocampal CA1, and auditory cortex (AC), and (5) stress priming to investigate the influence of corticosteroid on trauma-induced brain responses. We observed that IHC ribbon loss (deafferentation) leads to tinnitus when ABR functions remain reduced and Arc is not mobilized in the hippocampal CA1 and AC. If, however, ABR waves are functionally restored and Arc is mobilized, tinnitus does not occur. Both central response patterns were found to be independent of a profound threshold loss and could be shifted by the corticosterone level at the time of trauma. We, therefore, discuss the findings in the context of a history of stress that can trigger either an adaptive or nonadaptive brain response following injury. © 2012 Springer Science+Business Media New York.This work was supported by the Marie Curie Research Training Network CavNET MRTN-CT-2006-035367, Deutsche Forschungsgemeinschaft DFG-Kni-316-4-1, and Hahn Stiftung (Index AG).Peer Reviewe
Detection of Excitatory and Inhibitory Synapses in the Auditory System Using Fluorescence Immunohistochemistry and High-Resolution Fluorescence Microscopy
No full textUnveiling the frames of German identity: A sociohistorical analysis of in-group/out-group relations
No full textTreball Final del Màster Universitari en Estudis Internacionals de Pau, Conflictes i Desenvolupament (Pla de 2013). Codi: SBG119. Curs acadèmic 2014-2015This thesis argues that the German identity was constructed on the foundation of a rigid
and modern worldview that characterizes identity as fixed and exclusive and thus helped perpetuate
in-group/out-group relationships as binary oppositions such as white German and different
Other. It explores how key sociohistorical events are related to the construction of the
German in-group identity and how uneven power dynamics affect belonging. The author
identifies whiteness as identity privilege and as characteristic of a racialized German identity,
which reinforces the in-group/out-group binary. Furthermore, bridging the analysis to Europe´s
current refugee situation that challenges the German identity, this thesis argues there is
a potential for a transformative shift from an exclusive to a more inclusive identity. It explores
a process of de-centering and reframing of the German in-group identity in order to embrace
the negotiation of difference in Germany.Esta tesis argumenta que la identidad alemana fue construida sobre la base de una visión
del mundo rígida y moderna que caracteriza identidad como algo fijo y exclusivo y de este
modo ayudó a perpetuar las relaciones in-group/out-group como oposiciones binarias de
blanc@ Alemán@ y diferente Otr@. Se explora la relación de acontecimientos socio histórico
claves con la construcción de la identidad alemana como in-group y cómo dinámicas de poder
desiguales afectan la pertenencia. La autora identifica blancura como privilegio identitario y
como característica de una identidad alemana racial que refuerza el binario de in-group/outgroup.
Además, conectando el análisis con la situación actual de los refugiados en Europa que
desafía la identidad alemana, esta tesis argumenta que hay un potencial de transformación de
una identidad exclusiva hacia una identidad más inclusiva. Se explora un proceso de descentramiento
y replanteamiento de la identidad alemana como in-group con el fin de abarcar la
negociación de diferencia en Alemania.Die vorliegende Arbeit argumentiert, dass die deutsche Identität auf einer starren und
modernen Weltansicht begründet ist, welche die Identität als etwas Feststehendes und Exklusives
definiert und somit dazu beiträgt, dass in-group/out-group Beziehungen, wie weiße
Deutsche und andere, als binäre Gegensätze weiterbestehen bleiben. Die Arbeit analysiert,
inwiefern sozialhistorische Schlüsselereignisse mit der Begründung der deutschen in-group
Identität zusammenhängen und wie ungleich verteilte Machtverhältnisse sich auf die Zugehö-
rigkeit auswirken. Die Autorin identifiziert Weiß-sein als Identitätsprivileg und als Charakteristik
für eine rassifizierte deutsche Identität, welche die Binarität der in-group/out-group weiter
unterstützt. Unter Bezugnahme auf die aktuelle Flüchtlingssituation in Europa, welche die
deutsche Identität derzeit vor Herausforderungen stellt, sieht die Autorin das Potenzial für die
Wandlung weg von einem exkludierenden und hin zu einem mehr inkludierenden Identitätsverständnis.
Die Arbeit untersucht den Prozess der Dezentrierung und Neuausrichtung der
deutschen in-group Identität um einer Verständigung von Verschiedenheit offen begegnen zu
können
Deletion of BDNF in Pax2 Lineage-Derived Interneuron Precursors in the Hindbrain Hampers the Proportion of Excitation/Inhibition, Learning, and Behavior
No full text© 2021 Eckert, Marchetta, Manthey, Walter, Jovanovic, Savitska, Singer, Jacob, Rüttiger, Schimmang, Milenkovic, Pilz and Knipper.Numerous studies indicate that deficits in the proper integration or migration of specific GABAergic precursor cells from the subpallium to the cortex can lead to severe cognitive dysfunctions and neurodevelopmental pathogenesis linked to intellectual disabilities. A different set of GABAergic precursors cells that express Pax2 migrate to hindbrain regions, targeting, for example auditory or somatosensory brainstem regions. We demonstrate that the absence of BDNF in Pax2-lineage descendants of BdnfPax2KOs causes severe cognitive disabilities. In BdnfPax2KOs, a normal number of parvalbumin-positive interneurons (PV-INs) was found in the auditory cortex (AC) and hippocampal regions, which went hand in hand with reduced PV-labeling in neuropil domains and elevated activity-regulated cytoskeleton-associated protein (Arc/Arg3.1; here: Arc) levels in pyramidal neurons in these same regions. This immaturity in the inhibitory/excitatory balance of the AC and hippocampus was accompanied by elevated LTP, reduced (sound-induced) LTP/LTD adjustment, impaired learning, elevated anxiety, and deficits in social behavior, overall representing an autistic-like phenotype. Reduced tonic inhibitory strength and elevated spontaneous firing rates in dorsal cochlear nucleus (DCN) brainstem neurons in otherwise nearly normal hearing BdnfPax2KOs suggests that diminished fine-grained auditory-specific brainstem activity has hampered activity-driven integration of inhibitory networks of the AC in functional (hippocampal) circuits. This leads to an inability to scale hippocampal post-synapses during LTP/LTD plasticity. BDNF in Pax2-lineage descendants in lower brain regions should thus be considered as a novel candidate for contributing to the development of brain disorders, including autism.We acknowledge grants from the Deutsche Forschungsgemeins-chaft FOR 2060 project RU 713/3-2 (WS and LR), GRK 2381 (PM), SPP 1608 RU 316/12-1 (PE and LR), MI 954/3-1 (IM and SJ), KN 316/12-1 (MM and MK), BFU2016-76580-P (TS), and NIH NIMH 1R01MH106623 (MJ)
Effect of moisture on the nonlinear viscoelastic fracture behavior of polymer nanocompsites: a finite deformation phase-field model
No full textThe mechanisms underlying damage in high-performance polymer nanocomposites are remarkably affected by hygrothermal conditions. In this study, we develop a phase-field formulation to investigate the influence of hygrothermal conditions on the nonlinear viscoelastic fracture behavior of epoxy resins and their nanocomposites at finite deformation. For this, the Helmholtz free energy, capturing the effect of temperature and moisture and nanoparticle contents, is defined based on an additive decomposition of the energy into an equilibrium, a non-equilibrium, and a volumetric contribution with different definitions under tensile and compressive loading. The coupled displacement phase-field problem is solved using a quasi-Newton monolithic algorithm and a staggered solution scheme. Numerical examples show that the monolithic algorithm is more efficient. Simulations are performed to investigate the effect of temperature, deformation rate, and moisture content on the force–displacement response of boehmite nanoparticle/epoxy samples in benchmark numerical problems. Comparing numerical predictions and experimental data for compact-tension tests shows good agreement at different nanoparticle contents. Also, the model’s capability to predict fracture patterns is evaluated using simulations of single-edge notched nanocomposite plates under tensile and shear loading. © 2022, The Author(s)
BDNF-Live-Exon-Visualization (BLEV) Allows Differential Detection of BDNF Transcripts in vitro and in vivo
No full textBdnf exon-IV and exon-VI transcripts are driven by neuronal activity and are involved in pathologies related to sleep, fear or memory disorders. However, how their differential transcription translates activity changes into long-lasting network changes is elusive. Aiming to trace specifically the network controlled by exon-IV and -VI derived BDNF during activity-dependent plasticity changes, we generated a transgenic reporter mouse for BDNF-live-exon-visualization (BLEV), in which expression of Bdnf exon-IV and -VI can be visualized by co-expression of CFP and YFP. CFP and YFP expression was differentially activated and targeted in cell lines, primary cultures and BLEV reporter mice without interfering with BDNF protein synthesis. CFP and YFP expression, moreover, overlapped with BDNF protein expression in defined hippocampal neuronal, glial and vascular locations in vivo. So far, activity-dependent BDNF cannot be explicitly monitored independent of basal BDNF levels. The BLEV reporter mouse therefore provides a new model, which can be used to test whether stimulus-induced activity-dependent changes in BDNF expression are instrumental for long-lasting plasticity modifications
Specific synaptopathies diversify brain responses and hearing disorders: you lose the gain from early life
No full textVulnerability of hearing loss over age subsequent to the deletion of BDNF or CaV1.2 in the Cochlea
No full textResumen del póster presentado al 37th MidWinter Meeting of the Association for Research in Otorhinolaryngology celebrado en San Diego (US) del 22 al 26 de febrero de 2014.-- et al.[Background]: We recently showed that tissue-specific deletion of brain-derived neurotrophic factor (BDNF) in the cochlea prevents loss of thresholds and auditory brainstem response (ABR), and loss of inner hair cell (IHC) synaptic ribbons after exposure to traumatizing sound (Zuccotti et al., 2012; Journal of Neuroscience, 32, 25, 8545-53). These effects could be partly mimicked by the deletion of L-type voltage-gated calcium channel CaV1.2 in the cochlea (Zuccotti et al., 2013; Frontiers in molecular neuroscience, 6). The present study aimed to assess if deletion of BDNF or CaV1.2 in the cochlea alters the vulnerability of hearing over age. [Methods]: We compared the hearing function by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements on young and aged (1) conditional BDNFPax2 KO mice (Zuccotti et al., 2012) with the deletion of BDNF in the whole cochlea, the dorsal cochlear nucleus, and inferior colliculus, and (2) conditional CaV1.2Pax2 KO mice (Zuccotti et al., 2013) with deletion CaV1.2 in the same tissues as in the BDNFPax2 KO mice. We furthermore analyzed the influence of acoustic noise exposure on hearing loss.[Results]: Hearing function of both young and aged BDNFPax2KO and CaV1.2Pax2 KO mice were compared and related to outer hair cell (OHC) function and IHC synaptic structures. Suprathreshold ABR was analyzed in relation to young and aged mice. An interesting differential role of BDNF and CaV1.2 in the cochlea related to hair cell synaptic formation for sound processing became evident. [Conclusion]: We discuss the results in the context of a differential role
of BDNF and CaV1.2 for hair cell and neuronal vulnerability during aging.Peer Reviewe
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