The role of oxytocin in terror management processes.

Research on terror management theory found evidence for the idea that attachment and interpersonal touch attenuate existential concerns and worldview defense reactions after mortality salience. Oxytocin, on the other hand, is known for stimulating the attachment system. Therefore, we hypothesized that worldview defense reactions after mortality salience would be attenuated under oxytocin. In the present study, participants administered oxytocin or placebo and performed a typical terror management paradigm: After visualizing death or a control topic, worldview defense reactions were assessed by evaluating the authors of a pro- and an anti-German essay. Overall, the results did not provide strong support for the hypothesis. There was no effect of mortality salience on the overall worldview defense measure and, importantly, no moderation by oxytocin. However, with regard to the sympathy dimension, the expected pattern was revealed: The pro- and anti-German authors were evaluated as more balanced under oxytocin after mortality salience, whereas this was not the case under placebo. This was due to more positive evaluations of the anti-German author in the oxytocin group. Although this specific result was not expected a priori, sympathy was the only trait among all worldview defense variables that referred to a social level. Therefore, it seems possible that oxytocin is able to buffer existential concerns, but only if they are socially relevant.

Oxytocin promotes action prediction.

The neuropeptide oxytocin (OT) has been suggested to facilitate social cognition and behavior. As predicting others' behavior is at the core of human social-cognitive abilities and is indispensable for successful social interaction, we hypothesized that OT would increase action prediction. To test this hypothesis, 61 male and female healthy participants self-administered OT or placebo intranasally and their anticipatory eye-movements were recorded using eye-tracking techniques. We found that the ability to predict others' future actions was enhanced following OT treatment. This effect was mediated by the time to the first anticipatory eye-movement suggesting that improved action prediction might operate by increased attention to social cues. These findings provide direct evidence for the role of OT in promoting perception and processing of social cues.

Optical control of GIRK channels using visible light.

G-protein coupled inwardly rectifying potassium (GIRK) channels are an integral part of inhibitory signal transduction pathways, reducing the activity of excitable cells via hyperpolarization. They play crucial roles in processes such as cardiac output, cognition and the coordination of movement. Therefore, the precision control of GIRK channels is of critical importance. Here, we describe the development of the azobenzene containing molecule VLOGO (Visible Light Operated GIRK channel Opener), which activates GIRK channels in the dark and is promptly deactivated when illuminated with green light. VLOGO is a valuable addition to the existing tools for the optical control of GIRK channels as it circumvents the need to use potentially harmful UV irradiation. We therefore believe that VLOGO will be a useful research tool for studying GIRK channels in biological systems.

Genetic predisposition for high stress reactivity amplifies effects of early-life adversity.

A dysregulation of the hypothalamus-pituitary-adrenocortical (HPA) axis and the experience of early-life adversity are both well-established risk factors for the development of affective disorders, such as major depression. However, little is known about the interaction of these two factors in shaping endophenotypes of the disease. Here, we studied the gene-environment interaction of a genetic predisposition for HPA axis dysregulation with early-life stress (ELS), assessing the short-, as well as the long-lasting consequences on emotional behavior, neuroendocrine functions and gene expression profiles. Three mouse lines, selectively bred for either high (HR), intermediate (IR), or low (LR) HPA axis reactivity, were exposed to one week of ELS using the limited nesting and bedding material paradigm. Measurements collected during or shortly after the ELS period showed that, regardless of genetic background, ELS exposure led to impaired weight gain and altered the animals' coping behavior under stressful conditions. However, only HR mice additionally showed significant changes in neuroendocrine stress responsiveness at a young age. Accordingly, adult HR mice also showed lasting consequences of ELS, including hyperactive stress-coping, HPA axis hyperreactivity, and gene expression changes in the Crh system, as well as downregulation of Fkbp5 in relevant brain regions. We suggest that the genetic predisposition for high stress reactivity interacts with ELS exposure by disturbing the suppression of corticosterone release during a critical period of brain development, thus exerting lasting programming effects on the HPA axis, presumably via epigenetic mechanisms. In concert, these changes lead to the emergence of important endophenotypes associated with affective disorders.

Optical control of neuronal activity using a light-operated GIRK channel opener (LOGO).

G-protein coupled inwardly rectifying potassium channels (GIRKs) are ubiquitously expressed throughout the human body and are an integral part of inhibitory signal transduction pathways. Upon binding of Gßγ subunits released from G-protein coupled receptors (GPCRs), GIRK channels open and reduce the activity of excitable cells via hyperpolarization. As such, they play a role in cardiac output, the coordination of movement and cognition. Due to their involvement in a multitude of pathways, the precision control of GIRK channels is an important endeavour. Here, we describe the development of the photoswitchable agonist LOGO (the Light Operated GIRK-channel Opener), which activates GIRK channels in the dark and is rapidly deactivated upon exposure to long wavelength UV irradiation. LOGO is the first K+ channel opener and selectively targets channels that contain the GIRK1 subunit. It can be used to optically silence action potential firing in dissociated hippocampal neurons and LOGO exhibits activity in vivo, controlling the motility of zebrafish larvae in a light dependent fashion. We envisage that LOGO will be a valuable research tool to dissect the function of GIRK channels from other GPCR dependent signalling pathways.