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Publications (3)11.42 Total impact

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    ABSTRACT: Manganese-enhanced MRI has recently become a valuable tool for the assessment of in vivo functional cerebral activity in animal models. As a result of the toxicity of manganese at higher dosages, fractionated application schemes have been proposed to reduce the toxic side effects by using lower concentrations per injection. Here, we present data on regional-specific manganese accumulation during a fractionated application scheme over 8 days of 30 mg/kg MnCl(2) , as well as on the clearance of manganese chloride over the course of several weeks after the termination of the whole application protocol supplying an accumulative dose of 240 mg/kg MnCl(2) . Our data show most rapid accumulation in the superior and inferior colliculi, amygdala, bed nucleus of the stria terminalis, cornu ammonis of the hippocampus and globus pallidus. The data suggest that no ceiling effects occur in any region using the proposed application protocol. Therefore, a comparison of basal neuronal activity differences in different animal groups based on locally specific manganese accumulation is possible using fractionated application. Half-life times of manganese clearance varied between 5 and 7 days, and were longest in the periaqueductal gray, amygdala and entorhinal cortex. As the hippocampal formation shows one of the highest T(1) -weighted signal intensities after manganese application, and manganese-induced memory impairment has been suggested, we assessed hippocampus-dependent learning as well as possible manganese-induced atrophy of the hippocampal volume. No interference of manganese application on learning was detected after 4 days of Mn(2+) application or 2 weeks after the application protocol. In addition, no volumetric changes induced by manganese application were found for the hippocampus at any of the measured time points. For longitudinal measurements (i.e. repeated manganese applications), a minimum of at least 8 weeks should be considered using the proposed protocol to allow for sufficient clearance of the paramagnetic ion from cerebral tissue. Copyright © 2012 John Wiley & Sons, Ltd.
    NMR in Biomedicine 11/2012; · 3.45 Impact Factor
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    ABSTRACT: Posttraumatic stress disorder (PTSD) is characterized by the presence of three major symptom clusters: persistent fear memories, hyperarousal, and avoidance. With a passage of time after the trauma, PTSD patients show an increase in unspecific fear and avoidance, a phenomenon termed "fear generalization". It is not clear whether fear generalization arises from the time-dependent growth of hyperarousal or changes in associative fear. The present study investigated behavioral and neuroanatomical correlates of non-associative and associative fear memory one week vs. one month after a trauma in a mouse model of PTSD with immediate vs. delayed foot shock application. The immediate shock procedure led to a lower contextual fear, but did not influence the hyperarousal (i.e. increased acoustic startle responses) assessed within the first week after the trauma. Only delayed shocked mice demonstrated generalization of contextual fear and an increase in generalized avoidance behavior, with no changes in hyperarousal one month after trauma. We observed the same increase in c-Fos expression following delayed and immediate shock presentation within the lateral, basolateral, central amygdala and CA1, CA3 and dentate gyrus of hippocampus, suggesting that all of these structures contribute to the development of hyperarousal. Only basolateral amygdala and dentate gyrus appeared to be additionally involved in encoding of contextual information. In summary, our results demonstrate the independence of associative and non-associative trauma-related fear. They support the hypothesis that generalized fear emerges in consequence of forgetting specific stimulus attributes associated with the shock context.
    Behavioural brain research 05/2012; 233(2):483-93. · 3.22 Impact Factor
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    ABSTRACT: Spatial navigation is a fundamental capability necessary in everyday life to locate food, social partners, and shelter. It results from two very different strategies: (1) place learning which enables for flexible way finding and (2) response learning that leads to a more rigid "route following." Despite the importance of knockout techniques that are only available in mice, little is known about mice' flexibility in spatial navigation tasks. Here we demonstrate for C57BL6/N mice in a water-cross maze (WCM) that only place learning enables spatial flexibility and relearning of a platform position, whereas response learning does not. This capability depends on an intact hippocampal formation, since hippocampus lesions by ibotenic acid (IA) disrupted relearning. In vivo manganese-enhanced magnetic resonance imaging revealed a volume loss of ≥60% of the hippocampus as a critical threshold for relearning impairments. In particular the changes in the left ventral hippocampus were indicative of relearning deficits. In summary, our findings establish the importance of hippocampus-dependent place learning for spatial flexibility and provide a first systematic analysis on spatial flexibility in mice.
    Frontiers in Behavioral Neuroscience 01/2012; 6:87. · 4.76 Impact Factor