Oliver Stork

Oliver Stork
Otto-von-Guericke-Universität Magdeburg | OvGU · Department of Genetics & Molecular Neurobiology

PhD

About

195
Publications
20,498
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Introduction
Oliver Stork currently works at the Department of Genetics & Molecular Neurobiology, Otto-von-Guericke-Universität Magdeburg. Oliver does research in Cell Biology, Genetics and Molecular Biology. His current projects deal with the role of inhibitory interneurons in memory storage and the molecular factors that control memory consolidation,

Publications

Publications (195)
Article
Full-text available
Remembering the location of food is essential for survival. Rodents and humans employ mainly hippocampus-dependent spatial strategies, but when being stressed they shift to striatum-mediated stimulus-based strategies. To investigate underlying brain circuits, we tested mice with a heightened stress susceptibility due to a lack of the GABA-synthetiz...
Preprint
Remembering the location of food is essential for survival. Rodents and humans employ mainly hippocampus-dependent spatial strategies, but when being stressed they shift to striatum-mediated stimulus-based strategies. To investigate underlying brain circuits, we tested mice with a heightened stress susceptibility due to a lack of the GABA-synthetiz...
Preprint
Full-text available
Generalization is a critical feature of aversive memories and significantly contributes to post-traumatic stress disorder (PTSD) pathogenesis. While fear memories over time tend to generalize across differences in the contextual background and even to novel contextual settings, this effect can be counteracted by exposure to controlled reminder sess...
Poster
Lower graphs: Long-term potentiation (LTP) induction in young animals is achieved regardless of changes in NPYergic neurotransmission with 4xTBS, marked by * p<0.05 (paired t-test; one-tailed). Besides the graphs: Example traces from 30 of Input-Output curve. Example traces are plotted in grey after TBS and in blue/red before. Young and aged mice d...
Article
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Background Early-life stress can leave persistent epigenetic marks that may modulate vulnerability to psychiatric conditions later in life, including anxiety, depression and stress-related disorders. These are complex disorders with both environmental and genetic influences contributing to their etiology. Methyl-CpG Binding Protein 2 (MeCP2) has be...
Article
Antibiotics are widely applied for the treatment of bacterial infections, but their long-term use may lead to gut flora dysbiosis and detrimental effects on brain physiology, behavior as well as cognitive performance. Still, a striking lack of knowledge exists concerning electrophysiological correlates of antibiotic-induced changes in gut microbiot...
Preprint
Full-text available
Antibiotics are widely applied for the treatment of bacterial infections, but their long-term use may lead to gut flora dysbiosis and detrimental effects on brain physiology, behavior as well as cognitive performance. Still, a striking lack of knowledge exists concerning electrophysiological correlates of antibiotic-induced changes in gut microbiot...
Article
Full-text available
A presynaptic active zone organizer protein Bassoon orchestrates numerous important functions at the presynaptic active zone. We previously showed that the absence of Bassoon exclusively in forebrain glutamatergic presynapses (BsnEmx1cKO) in mice leads to developmental disturbances in dentate gyrus (DG) affecting synaptic excitability, morphology,...
Article
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Duplications and deletions of short chromosomal fragments are increasingly recognized as the cause for rare neurodevelopmental conditions and disorders. The NDR2 gene encodes a protein kinase important for neuronal development and is part of a microduplication region on chromosome 12 that is associated with intellectual disabilities, autism and epi...
Article
Full-text available
A high degree of regional, temporal and molecular specificity is evident in the regulation of GABAergic signaling in stress-responsive circuitry, hampering the use of systemic GABAergic modulators for the treatment of stress-related psychopathology. Here we investigated the effectiveness of local intervention with the GABA synthetic enzymes GAD65 a...
Article
Errors yield unfavorable outcomes but also elicit adaptive mechanisms optimizing future behavior. Norman et al. demonstrate a previously unknown direct projection from medial frontal performance-monitoring areas in mice that modulate visual cortex network activity and enable post-error attentional adaptation.
Article
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The Met allele of the Val66Met SNP of the BDNF gene (rs6265) is associated with impaired activity-dependent release of brain-derived neurotrophic factor (BDNF), resulting in reduced synaptic plasticity, impaired glutamatergic neurotransmission, and morphological changes. While previous work has demonstrated Val66Met effects on magnetic resonance sp...
Article
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Fragile X-associated tremor/ataxia syndrome (FXTAS) is an incurable neurodegenerative disorder caused by expansion of CGG repeats in the FMR1 5’UTR. The RNA containing expanded CGG repeats (rCGGexp) causes cell damage by interaction with complementary DNA, forming R-loop structures, sequestration of nuclear proteins involved in RNA metabolism and i...
Article
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Early life stress is an important vulnerability factor for the development of anxiety disorders, depression and late‐onset cognitive decline. Recently we demonstrated that juvenile stress (JS) lastingly enhanced long‐term potentiation via reduction of steady‐state glutamine synthetase mRNA expression and the associated dysregulation of the astrocyt...
Article
Studies in humans and rodents suggest a critical role for the hippocampal formation in cognition and emotion, but also in the adaptation to stressful events. Successful stress adaptation promotes resilience, while its failure may lead to stress-induced psychopathologies such as depression and anxiety disorders. Hippocampal architecture and physiolo...
Article
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Deficits in arginine vasopressin (AVP) and oxytocin (OT), two neuropeptides closely implicated in the modulation of social behaviours, have been reported in some early developmental disorders and autism spectrum disorders. Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene are associated to Rett syndrome and other neuropsychiatric...
Article
Deficits in arginine vasopressin (AVP) and oxytocin (OT), two neuropeptides closely implicated in the modulation of social behaviours, have been reported in some early developmental disorders and autism spectrum disorders. Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene are associated to Rett syndrome and other neuropsychiatric...
Article
Full-text available
DNA methylation is a crucial epigenetic mark for activity-dependent gene expression in neurons. Very little is known about how synaptic signals impact promoter methylation in neuronal nuclei. In this study we show that protein levels of the principal de novo DNA-methyltransferase in neurons, DNMT3A1, are tightly controlled by activation of N-methyl...
Poster
Full-text available
These authors contributed equally to this work ‡ These authors share senior authorship Anxiety and inclusion load in the BLA is already evident but amenable to rescue Inducible P90CGG mouse model Scheme of the transgene activation by the Tet-On system P90CGG mouse model & induction schedule DOX induction timelines showing the DOX ON and OFF (wash-o...
Poster
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Introduction: Phytoestrogens are non-steroidal estrogen analogues and are found primarily in soy products. They have received increasing attention as dietary supplements for estrogen deficiency and as modulators of endogenous estrogen functions, including cognition and emotion. In addition to modifying the levels of circulating sex hormones, phytoe...
Poster
Full-text available
Impact of sex hormones and gender on memory formation, plasticity and excitability has been extensively studied. Apart from its direct effects on neuronal functions and plasticity, the sex hormone estrogen interacts with other neuromodulatory systems and alter the use of cognitive resources via regulation of circuit plasticity and excitability. One...
Article
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Reductions of glutamate acid decarboxylase (GAD67) and subsequent GABA levels have been consistently observed in neuropsychiatric disorders like schizophrenia and depression, but it has remained unclear how GABAergic dysfunction contributes to different symptoms of the diseases. To address this issue, we investigated male mice haplodeficient for GA...
Article
Full-text available
Only a minority of trauma-exposed individuals develops Posttraumatic stress disorder (PTSD) and active processes may support trauma resilience. Individual behavioral profiling allows investigating neurobiological alterations related to resilience or pathology in animal models of PTSD and is utilized here to examine the activation of different inter...
Article
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Amphisomes are organelles of the autophagy pathway that result from the fusion of autophagosomes with late endosomes. While biogenesis of autophagosomes and late endosomes occurs continuously at axon terminals, non-degradative roles of autophagy at boutons are barely described. Here, we show that in neurons BDNF/TrkB traffick in amphisomes that sig...
Article
Phytoestrogens comprise biologically active constituents of human and animal diet that can impact on systemic and local estrogen functions in the brain. Here we report on the importance of dietary phytoestrogens for maintaining activity in a brain circuit controlling aggressive and social behavior of male mice. After six weeks of low-phytoestrogen...
Article
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Pre-pubertal stress increases post-traumatic stress disorder (PTSD) susceptibility. We have previously demonstrated that enriched environment (EE) intervention immediately after pre-pubertal stress protects from the effects of trauma in adulthood. Here, we examined whether exposure to EE would also be beneficial if applied after exposure to trauma...
Article
A traumatic childhood is among the most important risk factors for developing stress-related psychopathologies such as posttraumatic stress disorder or depression later in life. However, despite the proven role of astrocytes in regulating transmitter release and synaptic plasticity, the contribution of astrocytic transmitter metabolism to such stre...
Article
Full-text available
The protein doublecortin is mainly expressed in migrating neuroblasts and immature neurons. The X-linked gene MECP2, associated to several neurodevelopmental disorders such as Rett syndrome, encodes the protein methyl-CpG-binding protein 2 (MeCP2), a regulatory protein that has been implicated in neuronal maturation and refinement of olfactory circ...
Preprint
Full-text available
DNA-methylation is a crucial epigenetic mark for activity-dependent gene expression in neurons. Very little is known how synaptic signals impact promoter methylation in neuronal nuclei. In this study we show that protein levels of the principal de novo DNA-methyltransferase in neurons, DNMT3a1, are tightly controlled by activation of N-methyl-D-asp...
Preprint
Full-text available
Amphisomes are transient organelles that derive from fusion of autophagosomes with late endosomes. They rapidly transform into degradative autolysosomes, whereas non-degradative roles of the autophagic pathway have been barely described. Here we show that in neurons BDNF/TrkB receptor bearing Rab7 / Light chain 3 (LC3) - positive amphisomes signal...
Article
Full-text available
The hippocampus plays a central role as a hub for episodic memory and as an integrator of multimodal sensory information in time and space. Thereby, it critically determines contextual setting and specificity of episodic memories. It is also a key site for the control of innate anxiety states and involved in psychiatric diseases with heightened anx...
Article
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The integrin LFA-1 (CD11a/CD18) plays a critical role in the interaction of T cells with antigen presenting cells (APCs) to promote lymphocyte differentiation and proliferation. This integrin can be present either in a closed or in an open active conformation and its activation upon T-cell receptor (TCR) stimulation is a critical step to allow inte...
Article
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Recent years have seen increased interest in psychopathologies related to trauma exposure. Specifically, there has been a growing awareness to posttraumatic stress disorder (PTSD) in part due to terrorism, climate change-associated natural disasters, the global refugee crisis, and increased violence in overpopulated urban areas. However, notwithsta...
Article
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Bassoon is a large scaffolding protein of the presynaptic active zone involved in the development of presynaptic terminals and in the regulation of neurotransmitter release at both excitatory and inhibitory brain synapses. Mice with constitutive ablation of the Bassoon (Bsn) gene display impaired presynaptic function, show sensory deficits and deve...
Article
Anxiety disorders are common and debilitating conditions with higher prevalence in women. However, factors that predispose women to anxiety phenotypes are not clarified. Here we investigated potential contribution of the single nucleotide polymorphism rs2236418 in GAD2 gene to changes in regional inhibition/excitation balance, anxiety-like traits,...
Article
Full-text available
The serine/threonine kinase Ndr2 has been shown to control the inside-out activation of the β1subunit of integrins and the formation of neurites in both primary neurons and neurally differentiated pheochromacytoma (PC12) cells. In this study, we demonstrate that Ndr2 kinase furthermore determines the substrate specificity of neurite extension in PC...
Article
Behavioural metaplasticity is evident in experience-dependent changes of network activity patterns in neuronal circuits that connect the hippocampus, amygdala and medial prefrontal cortex. These limbic regions are key structures of a brain-wide neural network that translates emotionally salient events into persistent and vivid memories. Communicati...
Article
Compartmentalization of calcium-dependent plasticity allows for rapid actin remodeling in dendritic spines. However, molecular mechanisms for the spatio-temporal regulation of filamentous actin (F-actin) dynamics by spinous Ca2+-transients are still poorly defined. We show that the postsynaptic Ca2+sensor caldendrin orchestrates nano-domain actin d...
Article
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Cholinergic neuromodulation in the hippocampus controls the salience of background context memory acquired in the presence of elemental stimuli predicting an aversive reinforcement. With pharmacogenetic inhibition we here demonstrate that hilar perforant path-associated (HIPP) cells of the dentate gyrus mediate the devaluation of background context...
Article
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The formation of fear memories is a powerful and highly evolutionary conserved mechanism that serves the behavioral adaptation to environmental threats. Accordingly, classical fear conditioning paradigms have been employed to investigate fundamental molecular processes of memory formation. Evidence suggests that a circadian regulation mechanism all...
Article
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Noonan syndrome (NS) is characterized by reduced growth, craniofacial abnormalities, congenital heart defects, and variable cognitive deficits. NS belongs to the RASopathies, genetic conditions linked to mutations in components and regulators of the Ras signaling pathway. Approximately 50% of NS cases are caused by mutations in PTPN11. However, the...
Data
Functional analysis of genes differentially regulated by activity in hippocampi of Ptpn11D61Y mice. (A) Molecular network covering the DEGs with highest scores. (B) Network of predicted upstream transcription regulators. (C) Network of upstream posttranscriptional and posttranslational regulators for all datasets. In all networks, nodes and edges r...
Data
List of DEGs that are commonly regulated between the datasets. List of DEGs that are commonly regulated for each analyzed dataset are provided. (XLSX)
Data
List of primers used for the validation of genes by qRT-PCR. (DOCX)
Data
Effect of network activity modulation on the nuclear pERK level in low-density hippocampal cultures from Ptpn11D61Y and controls. (A) Representative images of DIV14 neurons of both genotypes stained for pERK in the basal state, upon stimulation of neuronal network activity by application of 4AP/Bic for 30 min and after activity silencing using the...
Data
Time course of activity-induced expression of BDNF and Arc. (A) The expression of BDNF was quantified by qPCR in hippocampal slices harvested 1, 3 or 6 h after incubation of slices with ACFS containing 4AP/Bic. Significantly increased BDNF mRNA levels were detected 3 h after stimulation. qPCR was run on samples for each time point and treatment in...
Data
Surface and total synaptic expression of glutamate receptors. The statistical comparison of the surface and total synaptic expression of glutamate receptors subunits: The intensity of the specific synaptic immunofluorescence (S1.1) and the density of the staining i.e. number of puncta per 20 μm long segments of dendrites (S1.2) are shown here. Stat...
Data
List of DEGs for all analyzed datasets. Full lists of DEGs for Ptpn11D61Y B vs. control B (A), control S vs. B (B), Ptpn11D61Y S vs. B (C) and Ptpn11D61Y S vs. control S (D) including fold changes and ANOVA p-values are provided. (XLSX)