The big picture:Mary Dallman, a role model

Mary Dallman has left a legacy in neuroendocrinology, not only as the scientist who elaborated on new concepts such as rapid corticosteroid feedback pathways, but also as a role model, particularly for women who followed in her footsteps. In this contribution, I compare (i) the remarkable journey she made toward her position as the first female faculty member ever at the physiology department at USCF with that of generations after her; (ii) the contribution of our labs on rapid corticosteroid actions; and, (iii) finally, our experiences with unexpected findings for which one should always keep an open mind, a standpoint that was fervently advocated by Mary Dallman.</p

Corticosterone rapidly reduces glutamatergic but not GABAergic transmission in the infralimbic prefrontal cortex of male mice

Rapid non-genomic effects of corticosteroid hormones, affecting glutamatergic and GABAergic transmission, have been described for many limbic structures in the rodent brain. These rapid effects appear to be region specific. It is not always clear which (or even whether) corticosteroid receptor -the glucocorticoid receptor (GR) or mineralocorticoid receptor (MR)- initiate these rapid effects. In the hippocampus and amygdala membrane-associated MR, but also membrane-associated GR (in amygdala), are involved. Other studies indicate that the rapid modulation may be induced by transactivation of kinases, or other receptors, like the G-protein coupled estrogen receptor (GPER) which was recently found to bind the mineralocorticoid aldosterone. In the current study we explored, in young adult male C57Bl6 mice, possible rapid effects of corticosterone on layer 2/3 infralimbic-prefrontal cortex (IL-PFC) neurons. We show that corticosterone, via non-genomic MR activation, reduces the mEPSC -but does not affect mIPSC- frequency; we observed no effect on mEPSC or mIPSC amplitude. As a result, overall spontaneous activity in the IL-PFC is suppressed. A potential role of GPER cannot be excluded, since G-15, an antagonist of GPER, also prevented the rapid effects of corticosterone.</p

The neuro-symphony of stress.

The impact of stress on brain function is increasingly recognized. Various substances are released in response to stress and can influence distinct neuronal circuits, but the functional advantages of having such a diversity of stress mediators remain unclear. Individual neurotransmitter, neuropeptide and steroid stress mediators have specific spatial and temporal niches, but these niches also overlap. In addition, the effects of individual mediators on neuronal function and plasticity are integrated, and emerging evidence suggests that there is crosstalk between them. Together, this results in the stress instruments producing an orchestrated 'symphony' that enables fine-tuned responses to diverse challenges

LTP after Stress: Up or Down?

When an organism is exposed to a stressful situation, corticosteroid levels in the brain rise. This rise has consequences for behavioral performance, including memory formation. Over the past decades, it has become clear that a rise in corticosteroid level is also accompanied by a reduction in hippocampal long-term potentiation (LTP). Recent studies, however, indicate that stress does not lead to a universal suppression of LTP. Many factors, including the type of stress, the phase of the stress response, the area of investigation, type of LTP, and the life history of the organism determine in which direction LTP will be changed

Stress Research:Past, Present, and Future

This chapter starts with highlighting the evolution of the stress concept and the discovery of mediators that coordinate stress adaptation. Next, progress in the unraveling of the mechanism underlying the action of these stress mediators is discussed, focusing on glucocorticoids as the end product of the hypothalamus-pituitary-adrenal (HPA) axis. This action exerted by the glucocorticoids is mediated by a dual receptor system: mineralocorticoid (MR) and glucocorticoid receptors (GR). With these receptors as leading theme we present five highlights that illustrate the serendipitous nature of stress research. These five highlights are integrated in the final section which culminates in reflections on the role of stress in mental health. In these reflections we merge the mind-boggling complexity of molecular signaling pathways with neuroendocrine communication, integrating body and brain functions. The new insights will be used during the next decennium to target, in an individual-specific fashion, the stress system with the objective to enhance the quality of life.</p

Regulation of Excitatory Synapses and Fearful Memories by Stress Hormones

Memories for emotionally arousing and fearful events are generally well retained. From the evolutionary point of view this is a highly adaptive behavioral response aimed to remember relevant information. However, fearful memories can also be inappropriately and vividly (re)expressed, such as in posttraumatic stress disorder. The memory formation of emotionally arousing events is largely modulated by hormones, peptides, and neurotransmitters which are released during and after exposure to these conditions. One of the core reactions in response to a stressful situation is the rapid activation of the autonomic nervous system, which results in the release of norepinephrine in the brain. In addition, stressful events stimulate the hypothalamus–pituitary–adrenal axis which slowly increases the release of glucocorticoid hormones from the adrenal glands. Here we will review how glucocorticoids and norepinephrine regulate the formation of fearful memories in rodents and humans and how these hormones can facilitate the storage of information by regulating excitatory synapses

State anxiety and cortisol reactivity to skydiving in novice versus experienced skydivers

Previous studies have suggested that skydiving, a naturalistic stressor, is associated with increases in self-reported stress, anxiety and cortisol levels. However, it has not been established whether this stress reactivity is altered as a function of repeated exposure to skydiving. This is of interest due to previous observations that cortisol reactivity becomes habituated with repeated exposure to laboratory stressors, however, few studies have investigated such habituation to naturalistic stressors. State anxiety and cortisol reactivity to skydiving were measured in 11 first-time skydivers and 13 experienced skydivers (≥ 30 jumps, mean jumps = 397.6), who were to complete a solo skydive. The novice skydivers reported significantly greater levels of state anxiety prior to the jump; however, there were no differences in pre-jump levels of salivary cortisol. Both groups exhibited significantly elevated salivary cortisol levels immediately post-jump, relative to i) pre-jump and ii) recovery. However, the two groups were indistinguishable with regard to their cortisol reactivity to the skydive. These findings support previous research demonstrating that skydiving elicits acute cortisol activation. Further, they suggest that i) cortisol reactivity does not habituate in experienced jumpers, and ii) that there is lack of concordance between self-reported levels of anxiety and biological stress reactivity in experienced skydivers