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Search Results: 1 - 10 of 31013 matches for " Thomas Seidenbecher "
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Patterns of Coupled Theta Activity in Amygdala-Hippocampal-Prefrontal Cortical Circuits during Fear Extinction
J?rg Lesting, Rajeevan T. Narayanan, Christian Kluge, Susan Sangha, Thomas Seidenbecher, Hans-Christian Pape
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0021714
Abstract: Signals related to fear memory and extinction are processed within brain pathways involving the lateral amygdala (LA) for formation of aversive stimulus associations, the CA1 area of the hippocampus for context-dependent modulation of these associations, and the infralimbic region of the medial prefrontal cortex (mPFC) for extinction processes. While many studies have addressed the contribution of each of these modules individually, little is known about their interactions and how they function as an integrated system. Here we show, by combining multiple site local field potential (LFP) and unit recordings in freely behaving mice in a fear conditioning paradigm, that theta oscillations may provide a means for temporally and functionally connecting these modules. Theta oscillations occurred with high specificity in the CA1-LA-mPFC network. Theta coupling increased between all areas during retrieval of conditioned fear, and declined during extinction learning. During extinction recall, theta coupling partly rebounded in LA-mPFC and CA1-mPFC, and remained at a low level in CA1-LA. Interfering with theta coupling through local electrical microstimulation in CA1-LA affected conditioned fear and extinction recall depending on theta phase. These results support the hypothesis that theta coupling provides a means for inter-areal coordination in conditioned behavioral responsiveness. More specifically, theta oscillations seem to contribute to a population code indicating conditioned stimuli during recall of fear memory before and after extinction.
Directional Theta Coherence in Prefrontal Cortical to Amygdalo-Hippocampal Pathways Signals Fear Extinction
J?rg Lesting, Thiemo Daldrup, Venu Narayanan, Christian Himpe, Thomas Seidenbecher, Hans-Christian Pape
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077707
Abstract: Theta oscillations are considered crucial mechanisms in neuronal communication across brain areas, required for consolidation and retrieval of fear memories. One form of inhibitory learning allowing adaptive control of fear memory is extinction, a deficit of which leads to maladaptive fear expression potentially leading to anxiety disorders. Behavioral responses after extinction training are thought to reflect a balance of recall from extinction memory and initial fear memory traces. Therefore, we hypothesized that the initial fear memory circuits impact behavioral fear after extinction, and more specifically, that the dynamics of theta synchrony in these pathways signal the individual fear response. Simultaneous multi-channel local field and unit recordings were obtained from the infralimbic prefrontal cortex, the hippocampal CA1 and the lateral amygdala in mice. Data revealed that the pattern of theta coherence and directionality within and across regions correlated with individual behavioral responses. Upon conditioned freezing, units were phase-locked to synchronized theta oscillations in these pathways, characterizing states of fear memory retrieval. When the conditioned stimulus evoked no fear during extinction recall, theta interactions were directional with prefrontal cortical spike firing leading hippocampal and amygdalar theta oscillations. These results indicate that the directional dynamics of theta-entrained activity across these areas guide changes in appraisal of threatening stimuli during fear memory and extinction retrieval. Given that exposure therapy involves procedures and pathways similar to those during extinction of conditioned fear, one therapeutical extension might be useful that imposes artificial theta activity to prefrontal cortical-amygdalo-hippocampal pathways that mimics the directionality signaling successful extinction recall.
Social Defeat: Impact on Fear Extinction and Amygdala-Prefrontal Cortical Theta Synchrony in 5-HTT Deficient Mice
Venu Narayanan, Rebecca S. Heiming, Friederike Jansen, J?rg Lesting, Norbert Sachser, Hans-Christian Pape, Thomas Seidenbecher
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0022600
Abstract: Emotions, such as fear and anxiety, can be modulated by both environmental and genetic factors. One genetic factor is for example the genetically encoded variation of the serotonin transporter (5-HTT) expression. In this context, the 5-HTT plays a key role in the regulation of central 5-HT neurotransmission, which is critically involved in the physiological regulation of emotions including fear and anxiety. However, a systematic study which examines the combined influence of environmental and genetic factors on fear-related behavior and the underlying neurophysiological basis is missing. Therefore, in this study we used the 5-HTT-deficient mouse model for studying emotional dysregulation to evaluate consequences of genotype specific disruption of 5-HTT function and repeated social defeat for fear-related behaviors and corresponding neurophysiological activities in the lateral amygdala (LA) and infralimbic region of the medial prefrontal cortex (mPFC) in male 5-HTT wild-type (+/+), homo- (?/?) and heterozygous (+/?) mice. Naive males and experienced losers (generated in a resident-intruder paradigm) of all three genotypes, unilaterally equipped with recording electrodes in LA and mPFC, underwent a Pavlovian fear conditioning. Fear memory and extinction of conditioned fear was examined while recording neuronal activity simultaneously with fear-related behavior. Compared to naive 5-HTT+/+ and +/? mice, 5-HTT?/? mice showed impaired recall of extinction. In addition, 5-HTT?/? and +/? experienced losers showed delayed extinction learning and impaired recall of extinction. Impaired behavioral responses were accompanied by increased theta synchronization between the LA and mPFC during extinction learning in 5-HTT-/? and +/? losers. Furthermore, impaired extinction recall was accompanied with increased theta synchronization in 5-HTT?/? naive and in 5-HTT?/? and +/? loser mice. In conclusion, extinction learning and memory of conditioned fear can be modulated by both the 5-HTT gene activity and social experiences in adulthood, accompanied by corresponding alterations of the theta activity in the amygdala-prefrontal cortex network.
Activity Modes in Thalamocortical Relay Neurons are Modulated by Gq/G11 Family G-proteins – Serotonergic and Glutamatergic Signaling
Philippe Coulon,Tatyana Kanyshkova,Tilman Broicher,Thomas Munsch,Nina Wettschureck,Thomas Seidenbecher,Sven G. Meuth,Stefan Offermanns,Hans-Christian Pape,Thomas Budde
Frontiers in Cellular Neuroscience , 2010, DOI: 10.3389/fncel.2010.00132
Abstract: In thalamocortical relay (TC) neurons, G-protein-coupled receptors play an important part in the control of activity modes. A conditional Gαq knockout on the background of a constitutive Gα11 knockout (Gαq/Gα11?/?) was used to determine the contribution of Gq/G11 family G-proteins to metabotropic serotonin (5-HT) and glutamate (Glu) function in the dorsal part of the lateral geniculate nucleus (dLGN). In control mice, current clamp recordings showed that α-m-5-HT induced a depolarization of Vrest which was sufficient to suppress burst firing. This depolarization was concentration-dependent (100 μM: +6 ± 1 mV, n = 10; 200 μM: +10 ± 1 mV, n = 7) and had a conditioning effect on the activation of other Gαq-mediated pathways. The depolarization was significantly reduced in Gαq/Gα11?/? (100 μM: 3 ± 1 mV, n = 11; 200 μM: 5 ± 1 mV, n = 6) and was apparently insufficient to suppress burst firing. Activating Gαq-coupled muscarinic receptors affected the magnitude of α-m-5-HT-induced effects in a reciprocal manner. Furthermore, the depolarizing effect of mGluR1 agonists was significantly reduced in Gαq/Gα11?/? mice. Immunohistochemical stainings revealed binding of 5-HT2CR- and mGluR1α-, but not of 5-HT2AR-specific antibodies in the dLGN of Gαq/Gα11?/? mice. In conclusion, these findings demonstrate that transmitters of ascending brainstem fibers and corticofugal fibers both signal via a central element in the form of Gq/G11-mediated pathways to control activity modes in the TC system.
Effects of AKAP5 Pro100Leu Genotype on Working Memory for Emotional Stimuli
Sylvia Richter, Xenia Gorny, Judith Machts, Gusalija Behnisch, Torsten Wüstenberg, Maike C. Herbort, Thomas F. Münte, Constanze I. Seidenbecher, Bj?rn H. Schott
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0055613
Abstract: Recent investigations addressing the role of the synaptic multiadaptor molecule AKAP5 in human emotion and behavior suggest that the AKAP5 Pro100Leu polymorphism (rs2230491) contributes to individual differences in affective control. Carriers of the less common Leu allele show a higher control of anger as indicated by behavioral measures and dACC brain response on emotional distracters when compared to Pro homozygotes. In the current fMRI study we used an emotional working memory task according to the n-back scheme with neutral and negative emotional faces as target stimuli. Pro homozygotes showed a performance advantage at the behavioral level and exhibited enhanced activation of the amygdala and fusiform face area during working memory for emotional faces. On the other hand, Leu carriers exhibited increased activation of the dACC during performance of the 2-back condition. Our results suggest that AKAP5 Pro100Leu effects on emotion processing might be task-dependent with Pro homozygotes showing lower control of emotional interference, but more efficient processing of task-relevant emotional stimuli.
A Potential Role for a Genetic Variation of AKAP5 in Human Aggression and Anger Control
Sylvia Richter,Josep Marco-Pallares,Judith Machts,Ludger Sch?ls,Antoni Rodriguez-Fornells,Carsten Reissner,Torsten Wüstenberg,Hans-Jochen Heinze,Eckart D. Gundelfinger,Emrah Düzel,Thomas F. Münte,Constanze I. Seidenbecher,Bj?rn H. Schott
Frontiers in Human Neuroscience , 2011, DOI: 10.3389/fnhum.2011.00175
Abstract: The A-kinase-anchoring protein 5 (AKAP5), a post-synaptic multi-adaptor molecule that binds G-protein-coupled receptors and intracellular signaling molecules has been implicated in emotional processing in rodents, but its role in human emotion and behavior is up to now still not quite clear. Here, we report an association of individual differences in aggressive behavior and anger expression with a functional genetic polymorphism (Pro100Leu) in the human AKAP5 gene. Among a cohort of 527 young, healthy individuals, carriers of the less common Leu allele (15.6% allele frequency) scored significantly lower in the physical aggression domain of the Buss and Perry Aggression Questionnaire and higher in the anger control dimension of the state-trait anger expression inventory. In a functional magnetic resonance imaging experiment we could further demonstrate that AKAP5 Pro100Leu modulates the interaction of negative emotional processing and executive functions. In order to investigate implicit processes of anger control, we used the well-known flanker task to evoke processes of action monitoring and error processing and added task-irrelevant neutral or angry faces in the background of the flanker stimuli. In line with our predictions, Leu carriers showed increased activation of the anterior cingulate cortex (ACC) during emotional interference, which in turn predicted shorter reaction times and might be related to stronger control of emotional interference. Conversely, Pro homozygotes exhibited increased orbitofrontal cortex (OFC) activation during emotional interference, with no behavioral advantage. Immunohistochemistry revealed AKAP5 expression in post mortem human ACC and OFC. Our results suggest that AKAP5 Pro100Leu contributes to individual differences in human aggression and anger control. Further research is warranted to explore the detailed role of AKAP5 and its gene product in human emotion processing.
Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory
Adriana Barman,Sylvia Richter,Joram Soch,Torsten Wüstenberg,Marieke Klein,Anni Richter,Gusalija Behnisch,Emrah Düzel,Constanze I. Seidenbecher,Bj?rn H. Schott
Frontiers in Human Neuroscience , 2014, DOI: 10.3389/fnhum.2014.00260
Abstract: The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP) rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT) and the logical memory section of the Wechsler Memory Scale (WMS). Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI) studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e., the myopia risk allele) showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point toward pleitropic effects of RASGRF1 genetic variations on complex neural function in humans.
Membrane-Bound Catechol-O-Methyl Transferase in Cortical Neurons and Glial Cells is Intracellularly Oriented
Bj?rn H. Schott,Renato Frischknecht,Grazyna Debska-Vielhaber,Nora John,Gusalija Behnisch,Emrah Düzel,Eckart D. Gundelfinger,Constanze I. Seidenbecher
Frontiers in Psychiatry , 2010, DOI: 10.3389/fpsyt.2010.00142
Abstract: Catechol-O-methyl transferase (COMT) is involved in the inactivation of dopamine in brain regions in which the dopamine transporter (DAT1) is sparsely expressed. The membrane-bound isoform of COMT (MB-COMT) is the predominantly expressed form in the mammalian central nervous system (CNS). It has been a matter of debate whether in neural cells of the CNS the enzymatic domain of MB-COMT is oriented toward the cytoplasmic or the extracellular compartment. Here we used live immunocytochemistry on cultured neocortical neurons and glial cells to investigate the expression and membrane orientation of native COMT and of transfected MB-COMT fused to green fluorescent protein (GFP). After live staining, COMT immunoreactivity was reliably detected in both neurons and glial cells after permeabilization, but not on unpermeabilized cells. Similarly, autofluorescence of COMT-GFP fusion protein and antibody fluorescence showed overlap only in permeabilized neurons. Our data provide converging evidence for an intracellular membrane orientation of MB-COMT in neurons and glial cells, suggesting the presence of a DAT1-independent postsynaptic uptake mechanism for dopamine, prior to its degradation via COMT.
Global Chemical Leasing Award 2010  [PDF]
Thomas Jakl
Technology and Investment (TI) , 2011, DOI: 10.4236/ti.2011.21003
Abstract: The Global Chemical Leasing Award was presented for the first time in March 2010 to organizations, companies and individuals for their outstanding efforts to enhance the visibility of Chemical Leasing around the world and reward successful Chemical Leasing initiatives and implementation. Chemical Leasing is the new business model in the field of sound use of chemicals, initiated and subsidized by the Austrian Federal Ministry for Agriculture, Forestry, the Environment and Water Management and jointly promoted with UNIDO. The decisive new aspect of this business model, which distinguishes itself from the traditional supplier-user relation, is to make the service performed by the chemical substance the basis of payment for the business operation, e.g. according to cleaned area, treated number of pieces, or performed hours of operation (= unit of payment). In this way an efficient use of chemicals is in the interest of all parties involved. The award was jointly organized by UNIDO and the Austrian Federal Ministry for Agriculture, Forestry, the Environment and Water Management. Organizations, companies and individuals worldwide were able to take part in the competition. The cases of the winners are described in detail and show the applicability of Chemical Leasing to the different industrial processes. Among these are water clarification and oil dehydration in Colombia, mineral water and beverage production in Serbia, oil & gas exploration and production and specifically deep gas field development projects in different places, industrial cleaning with solvents in Austria and textile dyeing in India.
The Effect of Different Movement Exercises on Cognitive and Motor Abilities  [PDF]
Monika Thomas
Advances in Physical Education (APE) , 2012, DOI: 10.4236/ape.2012.24030
Abstract: The influence of physical activity on motor and cognitive performance has been approved in several studies. However, it is still unclear which functions are affected, and why. It also remains unknown what type of physical training is best suitable. The present study focuses on special movement aspects based on the Brain Gym? program. Four groups of subjects (n = 64) participated in two experiments with pre-post intervention design. In experiment 1 two groups of subjects were exposed to a sensorimotor adaptation study design by executing center out pointing movements under distorted visual feedback conditions with their dominant and non-dominant arm to test for intermanual transfer (IMT) as pre- and posttest. The intervention in both groups consisted of specified movement exercises with the right and left extremities: participants of Experimental group executed movements crossing the body midline and participants of Control group movements without crossing the body midline. Results showed a decreased retention of adaptation but larger IMT for Experimental group during posttest. We conclude that movements crossing the body midline impede retention but enhance IMT of sensorimotor adaptation. A potential relationship to an improvement of communication between the cerebral hemispheres evoked by the movement exercises crossing the body midline is rather speculative. In experiment 2 two groups were exposed to the d2-test measuring concentration and attention and a dice-test testing for visual-spatial abilities as pre- and posttest. The interventions were similar to experiment 1. Results yielded no differences between groups such that different effects of both interventions could not have been shown.
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