Distinct Age-Specific Effects on Olfactory Associative Learning in C57BL/6 Substrains

C57BL/6 is the most widely used mouse strain in the laboratories. Two substrains of C57BL/6, C57BL/6J (B6J), and C57BL/6N (B6N) are well-known backgrounds for genetic modification and have been shown difference in quite a few tests, including open field test, rotarod test, and Morris water maze. How...

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Main Authors: Hung-Lun Chen, Chien-Fu F. Chen, Han-Bin Huang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Behavioral Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnbeh.2022.808978/full
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author Hung-Lun Chen
Chien-Fu F. Chen
Han-Bin Huang
author_facet Hung-Lun Chen
Chien-Fu F. Chen
Han-Bin Huang
author_sort Hung-Lun Chen
collection DOAJ
description C57BL/6 is the most widely used mouse strain in the laboratories. Two substrains of C57BL/6, C57BL/6J (B6J), and C57BL/6N (B6N) are well-known backgrounds for genetic modification and have been shown difference in quite a few tests, including open field test, rotarod test, and Morris water maze. However, difference between these two substrains in olfaction-dependent behaviors remains unknown. Here, we used olfactory two-alternative choice task, which is modified to have two training stages, to evaluate animals’ ability in instrumental learning and olfactory association. In the first (rule learning) stage, the mice were trained to use the operant chamber to collect water rewards. An odor cue was provided in the procedure, with no indication about reward locations. In the following (discrimination learning) stage, two odor cues were provided, with each indicating a specific water port. The animals were rewarded upon correct port choices following cue deliveries. We found that during young adulthood (7–10 weeks old), proportionally more B6J than B6N mice were able to pass rule learning (58.3% vs. 29.2%) and ultimately acquire this task (54.2% vs. 25%), with the two substrains showing similar pass rates in discrimination learning (92.9% vs. 85.7%). Surprisingly, at a more mature age (17 weeks old), this substrain difference disappeared. Mature B6N mice had a significant improvement in pass percentages of rule learning and overall task, whereas similar improvement was not observed in the B6J counterparts. Instead, mature B6J mice had an improved speed in rule learning and overall task. We further examined behavioral patterns of 8-week-old B6J and B6N mice in the olfactory habituation or dishabituation test. We observed normal olfactory habituation from subjects of both substrains, with the B6J mice exhibiting stronger investigative responses to newly presented odorants. These results reveal for the first time that B6J and B6N mice are different in acquisition processes of a behavioral task that requires instrumental learning and olfactory association, and that maturation appears to employ different effects on these two substrains during these processes. Furthermore, young adult B6J and B6N mice might be similar in olfactory habituation but different in the olfactory aspects of novelty seeking.
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spelling doaj.art-4d8e2209f9c547cbbb36e10c82ebf8452022-12-22T04:06:48ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532022-02-011610.3389/fnbeh.2022.808978808978Distinct Age-Specific Effects on Olfactory Associative Learning in C57BL/6 SubstrainsHung-Lun Chen0Chien-Fu F. Chen1Han-Bin Huang2Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, TaiwanGraduate Institute of Life Sciences, National Defense Medical Center, Taipei, TaiwanSchool of Public Health, National Defense Medical Center, Taipei, TaiwanC57BL/6 is the most widely used mouse strain in the laboratories. Two substrains of C57BL/6, C57BL/6J (B6J), and C57BL/6N (B6N) are well-known backgrounds for genetic modification and have been shown difference in quite a few tests, including open field test, rotarod test, and Morris water maze. However, difference between these two substrains in olfaction-dependent behaviors remains unknown. Here, we used olfactory two-alternative choice task, which is modified to have two training stages, to evaluate animals’ ability in instrumental learning and olfactory association. In the first (rule learning) stage, the mice were trained to use the operant chamber to collect water rewards. An odor cue was provided in the procedure, with no indication about reward locations. In the following (discrimination learning) stage, two odor cues were provided, with each indicating a specific water port. The animals were rewarded upon correct port choices following cue deliveries. We found that during young adulthood (7–10 weeks old), proportionally more B6J than B6N mice were able to pass rule learning (58.3% vs. 29.2%) and ultimately acquire this task (54.2% vs. 25%), with the two substrains showing similar pass rates in discrimination learning (92.9% vs. 85.7%). Surprisingly, at a more mature age (17 weeks old), this substrain difference disappeared. Mature B6N mice had a significant improvement in pass percentages of rule learning and overall task, whereas similar improvement was not observed in the B6J counterparts. Instead, mature B6J mice had an improved speed in rule learning and overall task. We further examined behavioral patterns of 8-week-old B6J and B6N mice in the olfactory habituation or dishabituation test. We observed normal olfactory habituation from subjects of both substrains, with the B6J mice exhibiting stronger investigative responses to newly presented odorants. These results reveal for the first time that B6J and B6N mice are different in acquisition processes of a behavioral task that requires instrumental learning and olfactory association, and that maturation appears to employ different effects on these two substrains during these processes. Furthermore, young adult B6J and B6N mice might be similar in olfactory habituation but different in the olfactory aspects of novelty seeking.https://www.frontiersin.org/articles/10.3389/fnbeh.2022.808978/fullC57BL/6olfactory two-alternative choice taskolfactory associative learningbrain maturationolfactory habituation/dishabituation test
spellingShingle Hung-Lun Chen
Chien-Fu F. Chen
Han-Bin Huang
Distinct Age-Specific Effects on Olfactory Associative Learning in C57BL/6 Substrains
Frontiers in Behavioral Neuroscience
C57BL/6
olfactory two-alternative choice task
olfactory associative learning
brain maturation
olfactory habituation/dishabituation test
title Distinct Age-Specific Effects on Olfactory Associative Learning in C57BL/6 Substrains
title_full Distinct Age-Specific Effects on Olfactory Associative Learning in C57BL/6 Substrains
title_fullStr Distinct Age-Specific Effects on Olfactory Associative Learning in C57BL/6 Substrains
title_full_unstemmed Distinct Age-Specific Effects on Olfactory Associative Learning in C57BL/6 Substrains
title_short Distinct Age-Specific Effects on Olfactory Associative Learning in C57BL/6 Substrains
title_sort distinct age specific effects on olfactory associative learning in c57bl 6 substrains
topic C57BL/6
olfactory two-alternative choice task
olfactory associative learning
brain maturation
olfactory habituation/dishabituation test
url https://www.frontiersin.org/articles/10.3389/fnbeh.2022.808978/full
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AT chienfufchen distinctagespecificeffectsonolfactoryassociativelearninginc57bl6substrains
AT hanbinhuang distinctagespecificeffectsonolfactoryassociativelearninginc57bl6substrains