Abstract
Glucocorticoids modulate diverse aspects of physiology and behavior, including energy homeostasis, stress response, and memory, through activation of the glucocorticoid receptor (GR). Light perception has profound effects on the production of glucocorticoids via functional connections of the retina to the hypothalamus-pituitary-adrenal axis. We report here that glucocorticoids can also signal in the reverse direction, i. e., regulate visual function in zebrafish, Danio rerio. The zebrafish GR mutant, grs357, harbors a missense mutation that completely blocks the transcriptional activity of GR. In this mutant, visual behavior was abolished following a period of darkness and recovered sluggishly after return to the light. Electrophysiological measurements showed that the photoresponse of the dark-adapted retina was reduced in the mutant and re-adapted to light with a substantial delay. Several gene products, including some that are important for dopaminergic signaling, were misregulated in grs357 mutants. We suggest that GR controls a gene network required for visual adaptation in the zebrafish retina and potentially integrates neuroendocrine and sensory responses to environmental changes.
Highlights
Glucocorticoids regulate diverse aspects of physiology, such as glucose metabolism, stress reactions, and neural plasticity (Kellendonk et al, 2002; Pecoraro et al, 2006; Krugers et al, 2012)
We suggest that glucocorticoid receptor (GR) controls a gene network required for visual adaptation in the zebrafish retina and potentially integrates neuroendocrine and sensory responses to environmental changes
When adapted to the ambient light in the recording setup, grs357 homozygous larvae showed a normal optokinetic response (OKR), which was comparable to homozygous WT and heterozygous siblings in amplitude of eye movements and frequency of saccades (Figure 1A; compare predark responses)
Summary
Glucocorticoids regulate diverse aspects of physiology, such as glucose metabolism, stress reactions, and neural plasticity (Kellendonk et al, 2002; Pecoraro et al, 2006; Krugers et al, 2012). In the HPA axis, the hypothalamus stimulates the pituitary to secrete adrenocorticotropic hormone (ACTH) into the bloodstream. ACTH acts on the adrenal gland (or its homolog the interrenal organ in teleosts), which synthesizes and secretes glucocorticoids (cortisol in fish and humans). Glucocorticoids in turn act broadly on peripheral tissues and the brain. Glucocorticoids provide negative feedback signals to the hypothalamus and the pituitary, terminating the stress response (Philips et al, 1997). Glucocorticoid levels in the blood oscillate in a circadian rhythm in all vertebrates, peaking at night or in the early morning and dropping in the afternoon (Baker and Rance, 1981)
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