Behavioral assessments of BTBR T+Itpr3tf/J mice by tests of object attention and elevated open platform: Implications for an animal model of psychiatric comorbidity in autism

Chao, Owen Y.; Yunger, Richelle; Yang, Yi

doi:10.1016/j.bbr.2018.03.014

Cited by 41 publications

(56 citation statements)

References 57 publications

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“…In the three-chamber sociability test (Fig. 3j), BTBR animals explored the stranger mouse and the empty cup indiscriminately, in line with early reports on their impaired social interaction [13,15]. Following the DHA treatment, they spent more time exploring the stranger than the empty cup (F 1,6 = 17.805, p = 0.006), reminiscent of normal behaviors of WT animals.…”

Section: Increased Gaba Release From Ins and Decreased Intrinsic Excisupporting

confidence: 70%

“…They display reduced sociability, altered ultrasonic vocalizations during development and increased self-grooming behavior. We have validated that they also exhibit the psychiatric comorbidity of ASD, including anxiety and attention deficit [15]. Additionally, these mice share similarities of anatomical changes with ASD patients [16], strengthening their applicability as an animal model for studying idiopathic autism [17].…”

Section: Introductionmentioning

confidence: 62%

“…Elevated open platform. The test exploited the innate tendency of fear of open space in rodents [15]. Animals were put onto an open platform that was elevated 30 cm for 5 min.…”

Section: Behavioral Testingmentioning

confidence: 99%

“…Object-based attention test. The test was to measure attentionassociated processes and/or working (short-term) object memory [15]. It was identical to a novel object-preference test, except with no time delay between learning and test trials.…”

Section: Behavioral Testingmentioning

confidence: 99%

“…For other analyses, n represented the number of mice. Sample sizes were decided by previous studies using similar protocols [15,31].…”

Section: Statisticsmentioning

confidence: 99%

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Targeting inhibitory cerebellar circuitry to alleviate behavioral deficits in a mouse model for studying idiopathic autism

Chao

Velasco

Pathak

et al. 2020

Neuropsychopharmacol.

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Autism spectrum disorder (ASD) encompasses wide-ranging neuropsychiatric symptoms with unclear etiology. Although the cerebellum is a key region implicated in ASD, it remains elusive how the cerebellar circuitry is altered and whether the cerebellum can serve as a therapeutic target to rectify the phenotype of idiopathic ASD with polygenic abnormalities. Using a syndromic ASD model, e.g., Black and Tan BRachyury T + Itpr3 tf /J (BTBR) mice, we revealed that increased excitability of presynaptic interneurons (INs) and decreased intrinsic excitability of postsynaptic Purkinje neurons (PNs) resulted in low PN firing rates in the cerebellum. Knowing that downregulation of Kv1.2 potassium channel in the IN nerve terminals likely augmented their excitability and GABA release, we applied a positive Kv1.2 modulator to mitigate the presynaptic over-inhibition and social impairment of BTBR mice. Selective restoration of the PN activity by a new chemogenetic approach alleviated core ASD-like behaviors of the BTBR strain. These findings highlight complex mechanisms converging onto the cerebellar dysfunction in the phenotypic model and provide effective strategies for potential therapies of ASD.

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Section: Increased Gaba Release From Ins and Decreased Intrinsic Excisupporting

confidence: 70%

Section: Introductionmentioning

confidence: 62%

“…Elevated open platform. The test exploited the innate tendency of fear of open space in rodents [15]. Animals were put onto an open platform that was elevated 30 cm for 5 min.…”

Section: Behavioral Testingmentioning

confidence: 99%

Section: Behavioral Testingmentioning

confidence: 99%

“…For other analyses, n represented the number of mice. Sample sizes were decided by previous studies using similar protocols [15,31].…”

Section: Statisticsmentioning

confidence: 99%

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Targeting inhibitory cerebellar circuitry to alleviate behavioral deficits in a mouse model for studying idiopathic autism

Chao

Velasco

Pathak

et al. 2020

Neuropsychopharmacol.

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Executive functions in agenesis of the corpus callosum: Working memory and sustained attention in the BTBR inbred mouse strain

et al. 2020

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Introduction Agenesis of the corpus callosum (AgCC) is characterized by the congenital partial or complete absence of the corpus callosum. Several strains of mice have been reported to carry AgCC, with the BTBR T+Itpr3tf/J (BTBR) inbred mouse strain consistently showing a complete absence of the corpus callosum, as well as a variable reduction in the size of the hippocampal commissure. While much research has focused on the social deficits of the BTBR strain, little research on its cognitive behavior has been conducted. The goal of our study was to compare two facets of executive functioning, spatial working memory, and sustained attention between the BTBR and C57BL/6J (B6) strains. Methods Spatial working memory was measured utilizing a delayed matching‐to‐position (DMTP) task and sustained attention was measured utilizing an operant task in which mice were trained to distinguish signal and nonsignal events. Results Both the BTBR and B6 mice demonstrated a predictable decline in performance on the DMTP task as the delay interval increased and predictable increase in performance on the sustained attention task as the duration of the signal event increased. Although no significant differences were found between strains on the performance of these tasks, there was a significant difference in learning the association between lever pressing and food reward. Histological investigation confirmed the complete absence of commissural fibers from the corpus callosum, but also the hippocampal commissure, counter to a previous study. Conclusion The results suggest spatial working memory and sustained attention are unaffected by the absence of these commissural fibers alone.

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A comparison of stress reactivity between BTBR and C57BL/6J mice: an impact of early-life stress

et al. 2023

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Behavioral assessments of BTBR T+Itpr3tf/J mice by tests of object attention and elevated open platform: Implications for an animal model of psychiatric comorbidity in autism

Cited by 41 publications

References 57 publications

Targeting inhibitory cerebellar circuitry to alleviate behavioral deficits in a mouse model for studying idiopathic autism

Targeting inhibitory cerebellar circuitry to alleviate behavioral deficits in a mouse model for studying idiopathic autism

Executive functions in agenesis of the corpus callosum: Working memory and sustained attention in the BTBR inbred mouse strain

A comparison of stress reactivity between BTBR and C57BL/6J mice: an impact of early-life stress

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