Optogenetically enhanced pituitary corticotroph cell activity post-stress onset causes rapid organizing effects on behaviour

Abstract

The anterior pituitary is the major link between nervous and hormonal systems, which allow the brain to generate adequate and flexible behaviour. Here, we address its role in mediating behavioural adjustments that aid in coping with acutely threatening environments. For this we combine optogenetic manipulation of pituitary corticotroph cells in larval zebrafish with newly developed assays for measuring goal-directed actions in very short timescales. Our results reveal modulatory actions of corticotroph cell activity on locomotion, avoidance behaviours and stimulus responsiveness directly after the onset of stress. Altogether, the findings uncover the significance of endocrine pituitary cells for rapidly optimizing behaviour in local antagonistic environments.

Performance on innate behaviour during early development as a function of stress level

“…Larval zebrafish execute complex visually-guided behaviours, including a robust optomotor reflex 9 , i.e., spontaneous swimming in the direction of large-field displacements in the visual field. They use hydrodynamic sensing, which provides many species of fish with benefits ranging from object detection to sensing conspecifics 10 , and their response to rising temperature 6 points to a fully functioning capacity for selecting best conditions in a thermal-gradient environment. Building on newly developed assays 6 , 11 – 14 and video tracking techniques, we assessed the larvae’s performance on a series of innate behaviours driven by visual, hydrodynamic and thermal inputs.…”

“…Zebrafish larvae are chosen because their hypothalamic-pituitary-interrenal (HPI) axis is homologous to the hypothalamic-pituitary-adrenal (HPA) axis 5 and their small size allows for the continuous measurement of behaviour with full environmental control, including stressor onset. Also, they offer an excellent handle for the analysis of stress reactions and for non-invasive brain imaging and behavioural genetics 6 – 8 . The results below provide direct evidence for the existence of an inverted-U shaped relationship between stress level and performance on innate behaviour.…”

Free cortisol/cortisone ratio in morning urine as a biomarker of health status in older Japanese adults

“…This is typically done by measuring cortisol before and after stress intervention, before and after waking up 16,41 , or by comparison with a control group in an experimental setting 42 . This study proposes a novel biomarker for good health based on the assumption that good health correlates with robust circadian rhythms and high levels of cortisol in the morning.…”

Active behaviour during early development shapes glucocorticoid reactivity

“…No data points or samples were excluded from analysis. Our sample sizes are generally employed in the field and based on previous publications 13,45 , statistical methods to predetermine sample size were not necessary. Normality was tested using the Shapiro–Wilk test.…”

“…However, it is still unclear how active responses to early life stress can reconfigure HPA axis function, pending a detailed functional evaluation of developmental programming of GC R . Larval zebrafish are excellent to address this knowledge gap due to their external development, their hypothalamic-pituitary-interrenal (HPI) axis, homologous to the mammalian HPA axis (Wenderlaar Bonga, 1997), their translucent body, ideal for non-invasive brain imaging and optogenetics (De Marco et al, 2016; Gahtan and Baier, 2004; Portugues et al, 2013), their small size, highly suitable for high-throughput screens with full environmental control, and the availability of tools and methods for identifying genetic and epigenetic modulators, including proteomic technology. Therefore, as a first step, we set out to determine the effect of early life stress on GC R and coping capacity in larval zebrafish.…”