Changing the nature of olfaction throughout life in a model vertebrate, Danio rerio
Creators: Shahriari, Arash
Publisher: name: University of Alberta Library
Year: 2024

<p>Animals use olfaction to receive invaluable information about their chemical environment. Chemical cues, also referred to as odourants, are detected by the olfactory system, which begins at the olfactory epithelium. Within this olfactory epithelium are olfactory sensory neurons (OSNs) that generate signals in response to odourants. Olfactory signals are transmitted to higher-order processing centers, which mediate behaviour. Olfaction develops early and changes throughout an animal’s lifespan as it further develops into adulthood until after a certain point when olfaction deteriorates due to aging-related processes. For my thesis, I used zebrafish to examine how olfaction changes throughout life. I also considered the complications of a more natural setting where multiple odourants are present.<br>
Animals encounter multiple odourants simultaneously. Often, these odourants evoke opposite responses when detected on their own. I used zebrafish to determine how animals may respond to a mixture containing an attracting and a repelling odourant. L-alanine was an attracting odourant while L-cysteine was a repelling odourant. When zebrafish detected L- alanine and L-cysteine together, they evoked an avoidance response. When the repelling odourant’s concentration decreased, the avoidance response towards the mixture became attraction.<br>
Animals imprint to odourants during early development. Correspondingly, long-term memories of odourants are formed and responses to these odourants change when re-exposed later in life. Olfactory imprinting may be disrupted by the addition of an odourant either during imprinting or during behavioural testing. I tested if zebrafish could imprint to single amino acids and to a binary amino acid mixture. Fish imprinted to L-leucine and L-lysine, but not to L-valine.However, fish that were exposed to L-leucine and L-lysine together did not imprint to either odourants separately or as a mixture, demonstrating that the complexity of the olfactory environment should be considered when examining imprinting.<br>
While imprinting shapes future olfactory-mediated behaviours, aging often causes hyposmia, which is a weakened olfactory sense. Hyposmia is associated with a thinning of the olfactory epithelium and a reduced number of OSNs, of which there are multiple classes. Each class is sensitive to a different subset of odourants. Two classes found across vertebrates are ciliated OSNs and microvillus OSNs, which in fish detect bile acids and amino acids, respectively. Aging studies have not yet examined if all OSN classes decrease in number equally. I examined if age has class-specific effects on OSN density with impacts on response to associated odourants. Even though olfactory epithelium thickness was unchanged, overall cell density decreased as fish aged. Class-specific changes to OSN density were observed as ciliated OSN density was the same across age, but microvillus density decreased with age. As zebrafish aged, only middle-aged fish demonstrated an increase in neuronal activation and elicited a behavioural response to a bile acid or an amino acid. Young- or old-aged fish displayed no response to the odourants. Therefore, olfaction may be most functional at middle age.<br>
Throughout an animal’s lifespan, olfaction faces chemical pressure from the environment such as from toxicant exposures. The olfactory epithelium is especially vulnerable to damage by toxicants as it directly interfaces the environment. Copper is a well-known neurotoxicant that enters the hydrosphere and induces apoptosis in the olfactory epithelium of fishes. Also, copper differentially affects ciliated and microvillus OSN density, as ciliated OSNs are more sensitive to the metal’s toxic effects than microvillus OSNs. Regardless, olfaction has remarkable resistance to toxicants from high biotransformation enzyme activity and OSN turnover rates. As animalsage, resistance to olfactory toxicity may weaken as biotransformation activity and OSN turnover rates decreases. I examined how age affects olfactory toxicity from copper exposures with a focus on OSN class-specific effects. Age did not change how copper affected the anatomy of the zebrafish olfactory epithelium as its thickness decreased while ciliated and microvillus OSN density was unchanged after copper exposures regardless of age. Differential toxicity was seen in aging fish as copper downregulated expression of genes involved in the signal-transduction pathway of ciliated OSNs only. Responses to an amino acid and a bile acid were seen in middle- aged fish only. Therefore, copper exposures only affected middle-aged fish responses to the odourants. While olfaction may be most functional at middle age, it is also at this age group when olfaction may be most vulnerable to disruption by toxicants.</p>