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A paradigm for exploring the impact of social isolation on olfactory sensitivity in mice

BACKGROUND: Mice have millions of olfactory sensory neurons that express one out of about 1,200 odorant receptor genes, giving them the ability to detect over 100,000 odorants. The activation of the sensory neurons is based on the different structural features of odor stimuli that each type of receptor has been genetically programmed to respond to. The activation at the level of the receptors corresponds to specific combinatorial codes for each odorant. Information from the receptors is sent to the olfactory bulb - where there is also a specific glomerular activation pattern for each odorant - and then to the olfactory tubercle, which plays a role in goal-directed behaviors and receives input from other parts of the brain that are essential for motivated behaviors. As a result of chronic social isolation, mice have been found to have impaired neurogenesis in their olfactory bulb, increased Tac2 expression, and decreased prefrontal cortex and hippocampal volumes. Since these neurological deficits alter the processing of olfactory information, using social isolation as a way to induce depression-like phenotypes in mice may provide insight into how changes in mental states are reflected in mouse behavior.
OBJECTIVE: To determine the relationship between odor concentration and olfactory sensitivity in mice, and how the relationship is impacted by social isolation.
METHODS: A total of 7 mice of either the C57BL/6J or tac1-cre strain aged 3-4 months were used. They underwent headplate surgery before going through habituation, after which they went through go/no-go task training. A custom 8-slot olfactometer and a behavioral box were used to run behavioral experiments, where up to 8 odorant tubes were placed in the olfactometer and mice were head-fixed in the behavioral box. Odorants were either blank odors made of only deionized water or different concentrations of n-butanol diluted in deionized water. With the blank odors as the “go” stimulus, the n-butanol odors as the “no-go” stimulus, and another blank odor as the “cheat” stimulus, mice went through go/no-go/cheat sessions over decreasing n-butanol concentrations. Python scripts were used to run experiments and collect data regarding the responses of the mice during each trial.
RESULTS: By the end of the training period, mice were able to achieve an accuracy of at least 85% during go/no-go tasks. There is an overall downward trend in the performances of mice over decreasing n-butanol concentrations, but there were also large and unexpected improvements in performance at lower concentrations before and after isolation. There were many fluctuations in the average latencies to odor on incorrect no-go trials over decreasing n-butanol concentrations before and after the isolation period. Although sample sizes for each sex were too low for statistical analyses, preliminary data suggests that at low odor concentrations, social isolation might lead to enhanced performance in males and decreased performance in females.
CONCLUSIONS: Mice can learn to associate novel odors with a water reward. Using social isolation as a way to induce depression in mice does not hinder mice from performing odor discrimination tasks. Conclusions cannot be made regarding the effect of social isolation on mouse olfactory sensitivity. Although there appears to be an improvement in performance as a result of isolation in male mice and a dampening of performance in female mice, further research will need to be conducted using larger sample sizes across both sexes.

Identiferoai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/48121
Date15 February 2024
CreatorsDaramola, Elizabeth
ContributorsBragdon, Beth, Murthy, Venkatesh
Source SetsBoston University
Languageen_US
Detected LanguageEnglish
TypeThesis/Dissertation

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