Author:
Yun Miru,Kim Eunjoon,Jung Min Whan
Abstract
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.
Funder
Institute for Basic Science
Publisher
Springer Science and Business Media LLC
Subject
Psychiatry and Mental health,Developmental Biology,Developmental Neuroscience,Molecular Biology
Reference117 articles.
1. American Psychiatric Association: Diagnostic and statistical manual of mental disorders (5th. ed). 2013.
2. Mundy P. Annotation: the neural basis of social impairments in autism: the role of the dorsal medial-frontal cortex and anterior cingulate system. J Child Psychol Psychiatry. 2003;44:793–809.
3. Hashem S, Nisar S, Bhat AA, Yadav SK, Azeem MW, Bagga P, Fakhro K, Reddy R, Frenneaux MP, Haris M. Genetics of structural and functional brain changes in autism spectrum disorder. Transl Psychiatry. 2020;10:229.
4. Yan Z, Rein B. Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications. Mol Psychiatry. 2021;27(1):1–21.
5. Schoenbaum G, Roesch MR, Stalnaker TA. Orbitofrontal cortex, decision-making and drug addiction. Trends Neurosci. 2006;29:116–24.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献