TY - JOUR A1 - Gromer, Daniel A1 - Kiser, Dominik P. A1 - Pauli, Paul T1 - Thigmotaxis in a virtual human open field test JF - Scientific Reports N2 - Animal models are used to study neurobiological mechanisms in mental disorders. Although there has been significant progress in the understanding of neurobiological underpinnings of threat-related behaviors and anxiety, little progress was made with regard to new or improved treatments for mental disorders. A possible reason for this lack of success is the unknown predictive and cross-species translational validity of animal models used in preclinical studies. Re-translational approaches, therefore, seek to establish cross-species translational validity by identifying behavioral operations shared across species. To this end, we implemented a human open field test in virtual reality and measured behavioral indices derived from animal studies in three experiments (N=31, N=30, and N=80). In addition, we investigated the associations between anxious traits and such behaviors. Results indicated a strong similarity in behavior across species, i.e., participants in our study-like rodents in animal studies-preferred to stay in the outer region of the open field, as indexed by multiple behavioral parameters. However, correlational analyses did not clearly indicate that these behaviors were a function of anxious traits of participants. We conclude that the realized virtual open field test is able to elicit thigmotaxis and thus demonstrates cross-species validity of this aspect of the test. Modulatory effects of anxiety on human open field behavior should be examined further by incorporating possible threats in the virtual scenario and/or by examining participants with higher anxiety levels or anxiety disorder patients. KW - anxiety KW - human behavior KW - anciety-like behavior KW - approach-avoidance conflict KW - elevated plus-maze KW - spatial navigation KW - mental disorders KW - fear KW - threat KW - circuits KW - reality KW - metaanalysis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259850 VL - 11 ER - TY - JOUR A1 - Ferero, Andrea A1 - Rivero, Olga A1 - Wäldchen, Sina A1 - Ku, Hsing-Ping A1 - Kiser, Dominik P. A1 - Gärtner, Yvonne A1 - Pennington, Laura S. A1 - Waider, Jonas A1 - Gaspar, Patricia A1 - Jansch, Charline A1 - Edenhofer, Frank A1 - Resink, Thérèse J. A1 - Blum, Robert A1 - Sauer, Markus A1 - Lesch, Klaus-Peter T1 - Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT Neuron Density and Prefrontal Cortex Innervation in the Mouse Brain JF - Frontiers in Cellular Neuroscience N2 - Background: During early prenatal stages of brain development, serotonin (5-HT)-specific neurons migrate through somal translocation to form the raphe nuclei and subsequently begin to project to their target regions. The rostral cluster of cells, comprising the median and dorsal raphe (DR), innervates anterior regions of the brain, including the prefrontal cortex. Differential analysis of the mouse 5-HT system transcriptome identified enrichment of cell adhesion molecules in 5-HT neurons of the DR. One of these molecules, cadherin-13 (Cdh13) has been shown to play a role in cell migration, axon pathfinding, and synaptogenesis. This study aimed to investigate the contribution of Cdh13 to the development of the murine brain 5-HT system. Methods: For detection of Cdh13 and components of the 5-HT system at different embryonic developmental stages of the mouse brain, we employed immunofluorescence protocols and imaging techniques, including epifluorescence, confocal and structured illumination microscopy. The consequence of CDH13 loss-of-function mutations on brain 5-HT system development was explored in a mouse model of Cdh13 deficiency. Results: Our data show that in murine embryonic brain Cdh13 is strongly expressed on 5-HT specific neurons of the DR and in radial glial cells (RGCs), which are critically involved in regulation of neuronal migration. We observed that 5-HT neurons are intertwined with these RGCs, suggesting that these neurons undergo RGC-guided migration. Cdh13 is present at points of intersection between these two cell types. Compared to wildtype controls, Cdh13-deficient mice display increased cell densities in the DR at embryonic stages E13.5, E17.5, and adulthood, and higher serotonergic innervation of the prefrontal cortex at E17.5. Conclusion: Our findings provide evidence for a role of CDH13 in the development of the serotonergic system in early embryonic stages. Specifically, we indicate that Cdh13 deficiency affects the cell density of the developing DR and the posterior innervation of the prefrontal cortex (PFC), and therefore might be involved in the migration, axonal outgrowth and terminal target finding of DR 5-HT neurons. Dysregulation of CDH13 expression may thus contribute to alterations in this system of neurotransmission, impacting cognitive function, which is frequently impaired in neurodevelopmental disorders including attention-deficit/hyperactivity and autism spectrum disorders. KW - serotonin KW - cadherin-13 (CDH13) KW - T-cadherin KW - neurodevelopment KW - psychiatric disorders KW - radial glia KW - dorsal raphe KW - prefrontal cortex Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170313 VL - 11 IS - 307 ER - TY - JOUR A1 - Kiser, Dominik P. A1 - Gromer, Daniel A1 - Pauli, Paul A1 - Hilger, Kirsten T1 - A virtual reality social conditioned place preference paradigm for humans: Does trait social anxiety affect approach and avoidance of virtual agents? JF - Frontiers in Virtual Reality N2 - Approach and avoidance of positive and negative social cues are fundamental to prevent isolation and ensure survival. High trait social anxiety is characterized by an avoidance of social situations and extensive avoidance is a risk factor for the development of social anxiety disorder (SAD). Therefore, experimental methods to assess social avoidance behavior in humans are essential. The social conditioned place preference (SCPP) paradigm is a well-established experimental paradigm in animal research that is used to objectively investigate social approach–avoidance mechanisms. We retranslated this paradigm for human research using virtual reality. To this end, 58 healthy adults were exposed to either a happy- or angry-looking virtual agent in a specific room, and the effects of this encounter on dwell time as well as evaluation of this room in a later test without an agent were examined. We did not observe a general SCPP effect on dwell time or ratings but discovered a moderation by trait social anxiety, in which participants with higher trait social anxiety spent less time in the room in which the angry agent was present before, suggesting that higher levels of trait social anxiety foster conditioned social avoidance. However, further studies are needed to verify this observation and substantiate an association with social anxiety disorder. We discussed the strengths, limitations, and technical implications of our paradigm for future investigations to more comprehensively understand the mechanisms involved in social anxiety and facilitate the development of new personalized treatment approaches by using virtual reality. KW - retranslational research KW - conditioned place preference KW - approach–avoidance KW - social anxiety KW - virtual reality KW - personality traits KW - individual differences Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-293564 SN - 2673-4192 VL - 3 ER -