The Olfactory System of Zebrafish as a Model for the Study of Neurotoxicity and Injury: Implications for Neuroplasticity and Disease

Abstract

The olfactory system, composed of the olfactory organs and the olfactory bulb, allows organisms to interact with their environment and through the detection of odor signals. Olfaction mediates behaviors pivotal for survival, such as feeding, mating, social behavior, and danger assessment. The olfactory organs are directly exposed to the milieu, and thus are particularly vulnerable to damage by environmental pollutants and toxicants, such as heavy metals, pesticides, and surfactants, among others. Given the widespread occurrence of olfactory toxicants, there is a pressing need to understand the effects of these harmful compounds on olfactory function. Zebrafish (Danio rerio) is a valuable model for studying human physiology, disease, and toxicity. Additionally, the anatomical components of the zebrafish olfactory system are similar to those of other vertebrates, and they present a remarkable degree of regeneration and neuroplasticity, making it an ideal model for the study of regeneration, reorganization and repair mechanisms following olfactory toxicant exposure. In this review, we focus on (1) the anatomical, morphological, and functional organization of the olfactory system of zebrafish; (2) the adverse effects of olfactory toxicants and injury to the olfactory organ; and (3) remodeling and repair neuroplasticity mechanisms following injury and degeneration by olfactory toxicant exposure.

Keywords: injury; neuroplasticity; olfactory bulb; olfactory organ; olfactory system; regeneration; toxicant; zebrafish.

Figure 1

Anatomical and morphological organization of the zebrafish olfactory system. (A) Localization of the olfactory system in zebrafish. Dorsal side is shown; rostral side is located upwards; (B) Olfactory organ morphology. Olfactory sensory epithelium arranged in lamellae is shown in black; (C) Olfactory epithelium (OE), composed of the following olfactory sensory neurons (OSNs): microvillous (mv); ciliated (cl); crypt (cr); kappe (kp); and pear (pr) OSNs. OSNs extend their axons to the olfactory bulb via the olfactory nerve (ON) to form discrete glomeruli; (D) Olfactory bulb organization in three laminae: olfactory nerve layer (ONL); glomerular layer (GL); and intracellular layer (ICL).

Figure 2

Odor-mediated behavioral tasks in zebrafish. (A) Odor-elicited swimming behaviors experimental setup. Individual fish are placed in either a rectangular or circular (not shown) experimental tank with two odorant delivery tubes collinearly positioned. An odorant is administered in one tube while water is simultaneously delivered in the other tube. Fish swimming patterns are recorded with a video camera (not shown); (B) Swimming trajectory of zebrafish after (top) odorant or (bottom) water exposure. Both swimming trajectory and time spent in each quadrant can be assessed with this test. This example depicts one of several swimming parameters that can be studied using this experimental setup.

Figure 3

Toxicant exposure and physical lesioning effects on the olfactory epithelium and its subsequent regeneration. (A) Degeneration and atrophy of the olfactory organ (OO), olfactory epithelium (OE), and olfactory sensory neurons (OSNs) following exposure to some toxicants and injury paradigms, some of which lead to olfactory dysfunction; (B) Effects of olfactory epithelium damage due to exposure to some toxicants and direct injury on the olfactory bulb, some of which lead to olfactory dysfunction; (C) Olfactory epithelium regeneration and repair following damage, leading to olfactory functional recovery; (D) Olfactory bulb regeneration and repair following damage to the OE, leading to olfactory functional recovery.