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Mice with an autism-associated R451C mutation in neuroligin-3 show intact attention orienting but atypical responses to methylphenidate and atomoxetine in the mouse-Posner task.

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Title: Mice with an autism-associated R451C mutation in neuroligin-3 show intact attention orienting but atypical responses to methylphenidate and atomoxetine in the mouse-Posner task.
Authors: Li, Shuting (AUTHOR), May, Carlos (AUTHOR), Pang, Terence Y. (AUTHOR), Churilov, Leonid (AUTHOR), Hannan, Anthony J. (AUTHOR), Johnson, Katherine A. (AUTHOR), Burrows, Emma L. (AUTHOR)
Source: Psychopharmacology. Mar2024, Vol. 241 Issue 3, p555-567. 13p.
Subjects: Methylphenidate, Atomoxetine, Mice, Task performance, Genetic mutation
Abstract: Rationale: Atypical attention orienting has been associated with some autistic symptoms, but the neural mechanisms remain unclear. The human Posner task, a classic attention orienting paradigm, was recently adapted for use with mice, supporting the investigation of the neurobiological underpinnings of atypical attention orienting in preclinical mouse models. Objective: The current study tested mice expressing the autism-associated R451C gene mutation in neuroligin-3 (NL3) on the mouse-Posner (mPosner) task. Methods: NL3R451C and wild-type (WT) mice were trained to respond to a validly or invalidly cued target on a touchscreen. The cue was a peripheral non-predictive flash in the exogenous task and a central spatially predictive image in the endogenous task. The effects of dopaminergic- and noradrenergic-modulating drugs, methylphenidate and atomoxetine, on task performance were assessed. Results: In both tasks, mice were quicker and more accurate in the validly versus invalidly cued trials, consistent with results in the human Posner task. NL3R451C and WT mice showed similar response times and accuracy but responded differently when treated with methylphenidate and atomoxetine. Methylphenidate impaired exogenous attention disengagement in NL3R451C mice but did not significantly affect WT mice. Atomoxetine impaired endogenous orienting in WT mice but did not significantly affect NL3R451C mice. Conclusions: NL3R451C mice demonstrated intact attention orienting but altered responses to the pharmacological manipulation of the dopaminergic and noradrenergic networks. These findings expand our understanding of the NL3R451C mutation by suggesting that this mutation may lead to selective alterations in attentional processes. [ABSTRACT FROM AUTHOR]
Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Mice with an autism-associated R451C mutation in neuroligin-3 show intact attention orienting but atypical responses to methylphenidate and atomoxetine in the mouse-Posner task.
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  Data: <searchLink fieldCode="AR" term="%22Li%2C+Shuting%22">Li, Shuting</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22May%2C+Carlos%22">May, Carlos</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pang%2C+Terence+Y%2E%22">Pang, Terence Y.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Churilov%2C+Leonid%22">Churilov, Leonid</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hannan%2C+Anthony+J%2E%22">Hannan, Anthony J.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Johnson%2C+Katherine+A%2E%22">Johnson, Katherine A.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Burrows%2C+Emma+L%2E%22">Burrows, Emma L.</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. Mar2024, Vol. 241 Issue 3, p555-567. 13p.
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  Data: <searchLink fieldCode="DE" term="%22Methylphenidate%22">Methylphenidate</searchLink><br /><searchLink fieldCode="DE" term="%22Atomoxetine%22">Atomoxetine</searchLink><br /><searchLink fieldCode="DE" term="%22Mice%22">Mice</searchLink><br /><searchLink fieldCode="DE" term="%22Task+performance%22">Task performance</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+mutation%22">Genetic mutation</searchLink>
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  Data: Rationale: Atypical attention orienting has been associated with some autistic symptoms, but the neural mechanisms remain unclear. The human Posner task, a classic attention orienting paradigm, was recently adapted for use with mice, supporting the investigation of the neurobiological underpinnings of atypical attention orienting in preclinical mouse models. Objective: The current study tested mice expressing the autism-associated R451C gene mutation in neuroligin-3 (NL3) on the mouse-Posner (mPosner) task. Methods: NL3R451C and wild-type (WT) mice were trained to respond to a validly or invalidly cued target on a touchscreen. The cue was a peripheral non-predictive flash in the exogenous task and a central spatially predictive image in the endogenous task. The effects of dopaminergic- and noradrenergic-modulating drugs, methylphenidate and atomoxetine, on task performance were assessed. Results: In both tasks, mice were quicker and more accurate in the validly versus invalidly cued trials, consistent with results in the human Posner task. NL3R451C and WT mice showed similar response times and accuracy but responded differently when treated with methylphenidate and atomoxetine. Methylphenidate impaired exogenous attention disengagement in NL3R451C mice but did not significantly affect WT mice. Atomoxetine impaired endogenous orienting in WT mice but did not significantly affect NL3R451C mice. Conclusions: NL3R451C mice demonstrated intact attention orienting but altered responses to the pharmacological manipulation of the dopaminergic and noradrenergic networks. These findings expand our understanding of the NL3R451C mutation by suggesting that this mutation may lead to selective alterations in attentional processes. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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              Text: Mar2024
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