How to run a brain bank. A report from the Austro-German brain bank

The sophisticated analysis of and growing information on the human brain requires that acquisition, dissection, storage and distribution of rare material are managed in a professional way. In this publication we present the concept and practice of our brain bank. Both brain tissue and information are handled by standardized procedures and flow in parallel from pathology to neuropathology and neurochemistry. Data concerning brain material are updated with clinical information gained by standardized procedures

Maladaptive plasticity in levodopa-induced dyskinesias and tardive dyskinesias: old and new insights on the effects of dopamine receptor pharmacology.

Maladaptive plasticity can be defined as behavioral loss or even development of disease symptoms resulting from aberrant plasticity changes in the human brain. Hyperkinetic movement disorders, in the neurological or psychiatric realms, have been associated with maladaptive neural plasticity that can be expressed by functional changes such as an increase in transmitter release, receptor regulation, and synaptic plasticity or anatomical modifications such as axonal regeneration, sprouting, synaptogenesis, and neurogenesis. Recent evidence from human and animal models provided support to the hypothesis that these phenomena likely depend on altered dopamine turnover induced by long-term drug treatment. However, it is still unclear how and where these altered mechanisms of cortical plasticity may be localized. This study provides an up-to-date overview of these issues together with some reflections on future studies in the field, particularly focusing on two specific disorders (levodopa-induced dyskinesias in Parkinson's disease patients and tardive dyskinesias in schizophrenic patients) where the modern neuroimaging approaches have recently provided new fundamental insights

The role of the hippocampus in generalizing configural relationships

The hippocampus has been implicated in integrating information across separate events in support of mnemonic generalizations. These generalizations may be underpinned by processes at both encoding (linking similar information across events) and retrieval (“on-the-fly” generalization). However, the relative contribution of the hippocampus to encoding- and retrieval-based generalizations is poorly understood. Using fMRI in humans, we investigated the hippocampal role in gradually learning a set of spatial discriminations and subsequently generalizing them in an acquired equivalence task. We found a highly significant correlation between individuals’ performance on a generalization test and hippocampal activity during the test, providing evidence that hippocampal processes support on-the-fly generalizations at retrieval. Within the same hippocampal region there was also a correlation between activity during the final stage of learning (when all associations had been learnt but no generalization was required) and subsequent generalization performance. We suggest that the hippocampus spontaneously retrieves prior events that share overlapping features with the current event. This process may also support the creation of generalized representations during encoding. These findings are supportive of the view that the hippocampus contributes to both encoding- and retrieval-based generalization via the same basic mechanism; retrieval of similar events sharing common features

Ulk4 regulates GABAergic signaling and anxiety-related behavior

Excitation/inhibition imbalance has been proposed as a fundamental mechanism in the pathogenesis of neuropsychiatric and neurodevelopmental disorders, in which copy number variations of the Unc-51 like kinase 4 (ULK4) gene encoding a putative Serine/Threonine kinase have been reported in approximately 1/1000 of patients suffering pleiotropic clinical conditions of schizophrenia, depression, autistic spectrum disorder (ASD), developmental delay, language delay, intellectual disability, or behavioral disorder. The current study characterized behavior of heterozygous Ulk4(+/tm1a) mice, demonstrating that Ulk4(+/tm1a) mice displayed no schizophrenia-like behavior in acoustic startle reactivity and prepulse inhibition tests or depressive-like behavior in the Porsolt swim or tail suspension tests. However, Ulk4(+/tm1a) mice exhibited an anxiety-like behavioral phenotype in several tests. Previously identified hypo-anxious (Atp1a2, Ptn, and Mdk) and hyper-anxious (Gria1, Syngap1, and Npy2r) genes were found to be dysregulated accordingly in Ulk4 mutants. Ulk4 was found to be expressed in GABAergic neurons and the Gad67⁺ interneurons were significantly reduced in the hippocampus and basolateral amygdala of Ulk4(+/tm1a) mice. Transcriptome analyses revealed a marked reduction of GABAergic neuronal subtypes, including Pvalb, Sst, Cck, Npy, and Nos3, as well as significant upregulation of GABA receptors, including Gabra1, Gabra3, Gabra4, Gabra5, and Gabrb3. This is the first evidence that Ulk4 plays a major role in regulating GABAergic signaling and anxiety-like behavior, which may have implications for the development of novel anxiolytic treatments

Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition

We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, i.e. deficient GABA transmission, within prefrontal cortex and hippocampus for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically-relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function); moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus, but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support that prefrontal and hippocampal neural disinhibition contributes to clinically relevant cognitive deficits, and we consider pharmacological strategies for ameliorating cognitive deficits by rebalancing disinhibition-induced aberrant neural activity

Beiträge zur Darstellung binärer und ternärer Nitride der Elemente Ga, Ru, Rh, Pd, Au, U

Die Dissertation beinhaltet Untersuchungen zur Darstellung binärer und ternärer Nitride der Elemente Ga, Ru, Rh, Pd, Au und U. Die Systeme Li-M-N (M = Ru, Rh, Pd, U), Na-M-N (M = Ga, Ru, Rh, Pd, U), Ca-U-N und Sr-Au-N werden diskutiert.Hervorzuheben sind die Verbindungen LiUN2, Li2UN2 und (Ca0,25U0,75)N0,96, die mittels Röntgenbeugungs- und teilweise mit Neutronenbeugungsmethoden charakterisiert wurden. In den Systemen Li-M-N (Ru, Rh, Pd) und Na-M-N (M = Ga, Ru, Rh, Pd, U) wurde die Bildung ternärer Nitride nicht beobachtet. Umsetzungen von NaNH2 mit Rh führten zur Bildung von Na3RhH6, das mit Röntgenbeugungsmethoden an Einkristallen untersucht werden konnte. Umsetzungen von Na/NaNH2/NaN3-Gemengen mit Ga führten in Abhängigkeit von der maximalen Reaktionstemperatur zur Bildung von einkristallinem a-GaN oder zur Bildung von NaGa(NH2)NH.Desweiteren konnten die Strukturen von SrAu5, Ga3Ni2, K11[(SiO4)2](OCN)2H mittels Einkristallröntgenstrukturanalyse bestimmt werden.This PhD thesis contents investigations of the synthesis of binary and ternary nitrides with the elements Ga, Ru, Rh, Pd, Au and U. The ternary systems Li-M-N (M = Ru, Rh, Pd, U), Na-M-N (M = Ga, Ru, Rh, Pd, U) Ca-U-N and Sr-Au-N were discussed.The compounds LiUN2, Li2UN2 and (Ca0,25U0,75)N0,96 were determined by using x-ray powder diffraction and neutron scattering methods.The formation of ternary nitrides were not investigated in the systems Li-M-N (Ru, Rh, Pd) and Na-M-N (M = Ga, Ru, Rh, Pd, U). Reactions of NaNH2 with Rh have shown the formation of Na3RhH6, which was determined with single crystal techniques. Reactions of Na/NaNH2/NaN3-mixtures with Ga were used to obtain crytalline a-GaN. At lower temperatures the formation of NaGa(NH2)NH was investigated.The structures of SrAu5, Ga3Ni2, K11[(SiO4)2](OCN)2H were determined by using single crystal methods

Effects of the neurogranin variant rs12807809 on thalamocortical morphology in schizophrenia

10.1371/journal.pone.0085603PLoS ONE812-POLN