Frontiers of stress research: the 2nd Munich Winter Conference on Stress

Challenges are the spice of life, for without a little bit of pressure, excitement and uncertainty, life would be a dull endeavor. However, chronic exposure to such stressful situations can in some cases lead to maladaptations and ultimately disease (De Kloet et al., 2005; Joëls & Baram, 2009). In the Munich Winter Stress Conference series (Schmidt & Chen, 2018), which took place for the second time in 2019, experts gather to discuss the latest advances in stress research, aiming to unravel the mechanisms underlying the regulation of the stress response and ultimately individual stress vulnerability or resilience. The last meeting took place at a time where we could all still meet in person, without social distancing, facial masks and the constant fear of getting a life-threatening viral infection. The Covid-19 pandemic has been, and continues to be, an unprecedented challenge, costing thousands of lives every day and causing exceptional suffering on a personal as well as societal level (Guessoum et al., 2020; Pfefferbaum & North, 2020). Besides the devastating health problems caused by this disease itself, the economic and social consequences are greater than anything witnessed in recent history (Vinkers et al., 2020). As a consequence, stress-induced illnesses are further on the rise and new advances in the field of stress research are dearly needed. The current special issue inspired by the 2nd Munich Winter Conference on Stress is therefore a timely collection of both review and research articles, illustrating many of the advances in this field of research.

Similar to the structure of the conference, the special issue starts off with an opinion paper by authors from the United States National Institute of Mental Health (NIMH), where the current director Joshua Gordon and colleagues detail their views on the future challenges and needed priorities in stress research (Simmons et al., 2020). In this overview article, the NIMH recognizes the central and important role of stress biology research in tackling the understanding and treatment of mental illnesses. Importantly, they outline aspects and focus areas of stress research that will help to channel the efforts and, in the end, improve translation from basic research to clinical applications and interventions. In line with these efforts, Damien Huzard from the University of Montpellier and colleagues present a review article tackling basic concepts of the stress response (Huzard et al., 2020). The authors propose that the stress response is continuously fine-tuned by neuronal activity, shaping the diversity of stress responses based on prior experience. Thus, while glucocorticoid actions are essential to maintain health, a disruption of this fine-tuned stress-response may lead to pathologies. The authors develop their concept spanning from molecular and genetic actions of glucocorticoids via the (mal)adaptive responses of individual cells, neuronal networks all the way to the function and behavior of an organism. Finally, the set of review articles is completed by Sofia Lopez and Shelly Flagel from the University of Michigan, who propose a role of glucocorticoid signaling in mediating cue-reward learning (Lopez & Flagel, 2020). Specifically, the authors suggest that glucocorticoids facilitate specifically dopamine-dependent forms of cue-reward learning, which are central and relevant for psychiatric disorders. The proposed framework may therefore be very useful in the testing of underlying mechanisms of complex neuropsychiatric disorders.

The special issue is rounded off by four research articles presenting highly relevant new data and research directions. Lotte van Doeselaar from the Max Planck Institute of Psychiatry in Munich presents together with her colleagues a validation of a chronic stress model in female mice (van Doeselaar et al., 2020). Stress research has in the past suffered from a sex bias, with most studies solely performed with male animals, thereby limiting the potential conclusions and translatability. Here they present a successful female adaptation of the very effective and widely used male mice model of chronic social defeat that will allow studying mechanisms of stress resilience in both sexes in parallel. A further technical advancement is presented by Qui Song from the University of Nijmegen. The group of Benno Roozendaal has been at the forefront of demonstrating that noradrenergic activation is essential in mediating the effects of emotional arousal on memory consolidation. Here they extend previous findings mainly from rat models to the mouse, illustrating that also in mice noradrenergic stimulation can enhance object recognition memory (Song et al., 2020). The study will pave the way for systematic investigations of the underlying neuronal circuitry, benefiting from experimental tools that are readily available in mice. Pascal Bielefeld from Carlos Fitzsimons’ lab at the University of Amsterdam addresses the question of adult neurogenesis. Building on previous work from the interaction of early life adversity and neurogenesis in the adult hippocampus, the group now extends their observations to another brain region, the hypothalamus (Bielefeld et al., 2021). The results are the first to indicate that early life stress can reduce neurogenesis in the adult hypothalamus of mice and may thereby shape the long-term metabolic effects of early life adversity. Last but not least, Susan Martelle from the group of James Herman at the University of Cincinnati presents a paper focusing on the role of the neuromodulatory peptide PACAP and its receptor, PAC1, in the prefrontal cortex on the stress response and fear memory (Martelle et al., 2021). By combining molecular analysis, pharmacological stimulation and behavioral readouts, they demonstrate a so far unappreciated role of PACAP influencing stress coping, anxiety-related behavior and HPA axis activity.

Overall, this special issue gives an overview of the diverse topics presented at the 2nd Munich Winter Conference on Stress. Unfortunately, the scheduled 3rd meeting of the series had to be postponed due to the Covid-19 pandemic but it will hopefully be held in March 2022. More information can be found on the conference web page: https://www.psych.mpg.de/2494539/winterkconference.