Maria Moltesen:
Central mechanisms underlying variability in the behavioral and neuroendocrine responses to stress in fish

Date: 31-01-2017    Supervisor: Torben Dabelsteen

Comparative models have revealed fundamental principles of nervous system function and organization. Teleost model systems have contributed essentially to our understanding of the evolution of the mechanisms involved in the behavioral and neuroendocrine stress response.

The purpose of the stress response is to protect or re-establish homeostasis in response to a perceived threat. A suite of neuroendocrine events aiming at enhancing an individual’s survival characterizes it. By filtering relevant sensory inputs and initiating stress responses, the brain is an essential organ in the regulation of the stress response. In mammals, the hippocampus and amygdala in the telencephalon play central roles in the process of discriminating sensory inputs that, potentially, will threaten the homeostasis of an individual. These regions are part of the limbic system, which interacts with the hypothalamic-pituitary-adrenal axis (HPA axis). This neuroendocrine stress axis includes corticotropin-releasing factor (CRF), which regulates the release of adrenocorticotropic hormone (ACTH) from the pituitary. A peptide is released to the circulation, inducing release of glucocorticoids from the adrenal cortex. The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) also plays an important role in the neuroendocrine stress response by controlling CRF release in hypothalamus. The transmission of 5-HT and CRF are under feedback control of glucocorticoids and interact with the stress response by affecting processes in the limbic system. In fish, the telencephalon contains regions that are functional homologues to the mammalian limbic system including amygdala and hippocampus. However, the involvement of this brain region in the regulation of the hypothalamicpituitary- interrenal (HPI) axis, the homologue of the mammalian HPA axis, is still not fully understood.

This PhD thesis investigates the role of the teleost telencephalon in regulation of the behavioral and neuroendocrine stress responses. Three studies were conducted:
Study I investigated the effect of acute and chronic stress on plasma cortisol, the major glucocorticoid in fish, and if these effects were related to changes in neurochemistry and gene expression in the telencephalon of rainbow trout (Oncorhynchus mykiss). The results showed that chronic stress affected HPI axis reactivity and serotonergic neurochemistry in the telencephalon. Moreover, effects of acute stress on post stress mRNA levels of the cortisol receptor; the mineralocorticoid receptor (MR) and the 5-HT receptor (5-HT1A) suggested that these receptors are involved in feedback mechanisms of the HPI axis.

Study II investigated if contrasting stress coping styles was reflected in telencephalic neurochemistry and gene expression in juvenile Gilthead seabream (Sparus aurata). The results showed that contrasting stress coping styles were reflected in differences in telencephalic serotonergic neurochemistry, independently of HPI axis reactivity.

Study III investigated if different behavioral responses to hypoxia in rainbow trout strains with contrasting stress coping styles were linked to differences in activation patterns in telencephalon and cognition. Neuronal activity in response to hypoxia stress, quantified by expression of the immediate early gene c-fos, revealed the engagement of distinct brain regions with limbic functions in the telencephalon. Moreover, differences in a conditioned-place-avoidance (CPA) test together with strain specific activation in Dm, an amygdaloid region, suggest that the telencephalon is involved in cognitive process underlying contrasting stress coping styles.

It is concluded that both individuality in the behavioral stress response and effects of chronic stress are reflected in 5-HT-ergic turnover in the telencephalon. Moreover, different activation patterns in the telencephalon during hypoxia in fish with contrasting stress coping styles further supports this brain region’s involvement in regulation of the behavioral and neuroendocrine stress responses. This is further supported by changes in post stress mRNA levels of MR and 5-HT1A, suggesting that telencephalon is involved in feedback regulation of the HPI axis.