Zebrafish Olfacto-Retinal Centrifugal Axon Projection and Distribution: Effects of Gonadotropin-Releasing Hormone and Dopaminergic Signaling

Abstract

The terminalis neurons (TNs) have been described in teleost species. In zebrafish, the TNs are located in the olfactory bulb. The TNs synthesize and release gonadotropin-releasing hormone (GnRH) as one of the major neurotransmitters. The TNs project axons to many brain areas, which include the neural retina. In the retina, the TN axons synapse with dopaminergic interplexiform cells (DA-IPCs) and retinal ganglion cells (RGCs). In this research, we examine the role of GnRH and dopaminergic signaling in TN axon projection to the retina using the transgenic zebrafish Tg(GnRH-3::GFP). While the TNs developed at 34 h postfertilization (hpf), the first TN axons were not detected in the retina until 48-50 hpf, when the first DA-IPCs were differentiated. In developing embryos, inhibition of retinal GnRH signaling pathways severely interrupted the projection of TN axons to the retina. However, inhibition of retinal dopaminergic signaling produced little effect on TN axon projection. In adult retinas, inactivation of GnRH receptors disrupted the patterns of TN axon distribution, and depletion of DA-IPCs abolished the TN axons. When DA-IPCs regenerated, the TN axons reappeared. Together, the data suggest that in developing zebrafish retinas GnRH signaling is required for TN axon projection, whereas in adult retinas activation of GnRH and dopaminergic signaling transduction is required for normal distribution of the TN axons.

Growth Hormone (GH) and Gonadotropin-Releasing Hormone (GnRH) in the Central Nervous System: A Potential Neurological Combinatory Therapy?

“…GnRH-R gene promoter activity was detected in the rat retina during embryonic development, implicating its action in the eye growth and differentiation [ 141 ]. In the zebrafish, GnRH signaling is required for proper axon projection of terminal neurons, and these cells synapse with interplexiform cells and retinal ganglion cells (RGCs) [ 156 ]. Recently, a report from Corchuelo et al [ 142 ] demonstrated that GnRH is involved in the neuromodulation of the retina, particularly in the final stages of maturation.…”

Sensory Integration: Cross-Modal Communication Between the Olfactory and Visual Systems in Zebrafish

“…et al 2015). The development of the ORC pathway is mediated by neural signals related to the neurogenesis and/or function of retinal DA-IPCs (Pfister et al 2015). In zebrafish, stimulation of the olfactory neurons alters the firing of TNs, which in turn decreases the release of dopamine from DA-IPCs and thereby increases retinal sensitivity (Maaswinkel and Li 2003;Huang et al 2005;Wang et al 2011).…”

“…These fish provide excellent tools for characterization of the development and function of the ORC pathway. Using Tg(GnRH-3::GFP) transgenic fish, Pfister et al (2015) examined the courses of TN axonal projection to the retina. In developing embryos, soon after the neurogenesis of TNs at approximately 1.5 days postfertilization, TN axons are observed in the brain.…”

“…In the retina, DA-IPCs are the only cell types that synthesize and release dopamine (Dowling 1991;Yazulla et al 1996). To study the possible roles of dopamine on TN axonal projection, Pfister et al (2015) examined the distribution of TN axons in adult zebrafish retinas in which DA-IPCs are degenerated and subsequently regenerated ( Figure 2C-F). DA-IPCs can be destroyed by intraocular injection of neurotoxin 6-hydroxydopamine (6-OHDA; Lin and Yazulla 1994;Li and Dowling 2000).…”

“…Abbreviations: d, day; dpi, days post injection; GFP, green fluorescent protein. Scale bar: 50 μm (modified fromPfister et al 2015).…”