Enhanced fear limits behavioral flexibility in Shank2-deficient mice
Abstract Background A core symptom of autism spectrum disorder (ASD) is repetitive and restrictive patterns of behavior. Cognitive inflexibility has been proposed as a potential basis for these symptoms of ASD. More generally, behavioral inflexibility has been proposed to underlie repetitive and res...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Molecular Autism |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13229-022-00518-1 |
| _version_ | 1797996126867030016 |
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| author | Miru Yun Eunjoon Kim Min Whan Jung |
| author_facet | Miru Yun Eunjoon Kim Min Whan Jung |
| author_sort | Miru Yun |
| collection | DOAJ |
| description | Abstract Background A core symptom of autism spectrum disorder (ASD) is repetitive and restrictive patterns of behavior. Cognitive inflexibility has been proposed as a potential basis for these symptoms of ASD. More generally, behavioral inflexibility has been proposed to underlie repetitive and restrictive behavior in ASD. Here, we investigated whether and how behavioral flexibility is compromised in a widely used animal model of ASD. Methods We compared the behavioral performance of Shank2-knockout mice and wild-type littermates in reversal learning employing a probabilistic classical trace conditioning paradigm. A conditioned stimulus (odor) was paired with an unconditioned appetitive (water, 6 µl) or aversive (air puff) stimulus in a probabilistic manner. We also compared air puff-induced eye closure responses of Shank2-knockout and wild-type mice. Results Male, but not female, Shank2-knockout mice showed impaired reversal learning when the expected outcomes consisted of a water reward and a strong air puff. Moreover, male, but not female, Shank2-knockout mice showed stronger anticipatory eye closure responses to the air puff compared to wild-type littermates, raising the possibility that the impairment might reflect enhanced fear. In support of this contention, male Shank2-knockout mice showed intact reversal learning when the strong air puff was replaced with a mild air puff and when the expected outcomes consisted of only rewards. Limitations We examined behavioral flexibility in one behavioral task (reversal learning in a probabilistic classical trace conditioning paradigm) using one ASD mouse model (Shank2-knockout mice). Thus, future work is needed to clarify the extent to which our findings (that enhanced fear limits behavioral flexibility in ASD) can explain the behavioral inflexibility associated with ASD. Also, we examined only the relationship between fear and behavioral flexibility, leaving open the question of whether abnormalities in processes other than fear contribute to behavioral inflexibility in ASD. Finally, the neurobiological mechanisms linking Shank2-knockout and enhanced fear remain to be elucidated. Conclusions Our results indicate that enhanced fear suppresses reversal learning in the presence of an intact capability to learn cue-outcome contingency changes in Shank2-knockout mice. Our findings suggest that behavioral flexibility might be seriously limited by abnormal emotional responses in ASD. |
| first_indexed | 2024-04-11T10:12:36Z |
| format | Article |
| id | doaj.art-2305b77dbd0046b3ad0e77dd2b8327d7 |
| institution | Directory Open Access Journal |
| issn | 2040-2392 |
| language | English |
| last_indexed | 2024-04-11T10:12:36Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Autism |
| spelling | doaj.art-2305b77dbd0046b3ad0e77dd2b8327d72022-12-22T04:30:03ZengBMCMolecular Autism2040-23922022-10-0113111810.1186/s13229-022-00518-1Enhanced fear limits behavioral flexibility in Shank2-deficient miceMiru Yun0Eunjoon Kim1Min Whan Jung2Department of Biological Sciences, Korea Advanced Institute of Science and TechnologyDepartment of Biological Sciences, Korea Advanced Institute of Science and TechnologyDepartment of Biological Sciences, Korea Advanced Institute of Science and TechnologyAbstract Background A core symptom of autism spectrum disorder (ASD) is repetitive and restrictive patterns of behavior. Cognitive inflexibility has been proposed as a potential basis for these symptoms of ASD. More generally, behavioral inflexibility has been proposed to underlie repetitive and restrictive behavior in ASD. Here, we investigated whether and how behavioral flexibility is compromised in a widely used animal model of ASD. Methods We compared the behavioral performance of Shank2-knockout mice and wild-type littermates in reversal learning employing a probabilistic classical trace conditioning paradigm. A conditioned stimulus (odor) was paired with an unconditioned appetitive (water, 6 µl) or aversive (air puff) stimulus in a probabilistic manner. We also compared air puff-induced eye closure responses of Shank2-knockout and wild-type mice. Results Male, but not female, Shank2-knockout mice showed impaired reversal learning when the expected outcomes consisted of a water reward and a strong air puff. Moreover, male, but not female, Shank2-knockout mice showed stronger anticipatory eye closure responses to the air puff compared to wild-type littermates, raising the possibility that the impairment might reflect enhanced fear. In support of this contention, male Shank2-knockout mice showed intact reversal learning when the strong air puff was replaced with a mild air puff and when the expected outcomes consisted of only rewards. Limitations We examined behavioral flexibility in one behavioral task (reversal learning in a probabilistic classical trace conditioning paradigm) using one ASD mouse model (Shank2-knockout mice). Thus, future work is needed to clarify the extent to which our findings (that enhanced fear limits behavioral flexibility in ASD) can explain the behavioral inflexibility associated with ASD. Also, we examined only the relationship between fear and behavioral flexibility, leaving open the question of whether abnormalities in processes other than fear contribute to behavioral inflexibility in ASD. Finally, the neurobiological mechanisms linking Shank2-knockout and enhanced fear remain to be elucidated. Conclusions Our results indicate that enhanced fear suppresses reversal learning in the presence of an intact capability to learn cue-outcome contingency changes in Shank2-knockout mice. Our findings suggest that behavioral flexibility might be seriously limited by abnormal emotional responses in ASD.https://doi.org/10.1186/s13229-022-00518-1Shank2Reversal learningFearClassical conditioning |
| spellingShingle | Miru Yun Eunjoon Kim Min Whan Jung Enhanced fear limits behavioral flexibility in Shank2-deficient mice Molecular Autism Shank2 Reversal learning Fear Classical conditioning |
| title | Enhanced fear limits behavioral flexibility in Shank2-deficient mice |
| title_full | Enhanced fear limits behavioral flexibility in Shank2-deficient mice |
| title_fullStr | Enhanced fear limits behavioral flexibility in Shank2-deficient mice |
| title_full_unstemmed | Enhanced fear limits behavioral flexibility in Shank2-deficient mice |
| title_short | Enhanced fear limits behavioral flexibility in Shank2-deficient mice |
| title_sort | enhanced fear limits behavioral flexibility in shank2 deficient mice |
| topic | Shank2 Reversal learning Fear Classical conditioning |
| url | https://doi.org/10.1186/s13229-022-00518-1 |
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