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

Maria Møller Moltesen

Abstract

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.
OriginalsprogEngelsk
ForlagDepartment of Biology, Faculty of Science, University of Copenhagen
StatusUdgivet - 2017

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