Touchscreen learning deficits and normal social approach behavior in the Shank3B model of Phelan-McDermid Syndrome and autism

Autor: Nycole A. Copping, Jill L. Silverman, Beth L. Onaga, Nathalie Buscher, Gillian M. Foley, Melanie D. Schaffler, Elizabeth L. Berg, Mu Yang
Rok vydání: 2015
Předmět:
0301 basic medicine
Male
Autism
Chromosomes
Human
Pair 22
Chromosome Disorders
Neuropsychological Tests
associative learning
Transgenic
Mice
0302 clinical medicine
Discrimination
Psychological
Discrimination
Psychology
Discrimination learning
SHANK3
Pediatric
Learning Disabilities
General Neuroscience
Cambridge Neuropsychological Test Automated Battery
Microfilament Proteins
Cognitive flexibility
Cognition
Mental Health
Autism spectrum disorder
Neurological
Visual Perception
Cognitive Sciences
Chromosome Deletion
Cognitive psychology
Human
Intellectual and Developmental Disabilities (IDD)
Phelan–McDermid Syndrome
Mice
Transgenic
Nerve Tissue Proteins
NIH Toolbox
Motor Activity
Basic Behavioral and Social Science
Chromosomes
Article
03 medical and health sciences
Behavioral and Social Science
medicine
Animals
mouse models
Autistic Disorder
Social Behavior
Phelan-McDermid Syndrome
Neurology & Neurosurgery
Animal
Neurosciences
Association Learning
medicine.disease
Associative learning
Brain Disorders
Disease Models
Animal
030104 developmental biology
Disease Models
Psychological
touchscreen
Pair 22
Neuroscience
030217 neurology & neurosurgery
Zdroj: Neuroscience. 345
ISSN: 1873-7544
Popis: SHANK3 is a synaptic scaffolding protein localized in the postsynaptic density and has a crucial role in synaptogenesis and neural physiology. Deletions and point mutations in SHANK3 cause Phelan-McDermid Syndrome (PMS), and have also been implicated in autism spectrum disorder (ASD) and intellectual disabilities, leading to the hypothesis that reduced SHANK3 expression impairs basic brain functions that are important for social communication and cognition. Several mouse models of Shank3 deletions have been generated, varying in the specific domain deleted. Here we report impairments in cognitive function in mice heterozygous for exon 13-16 (coding for the PDZ domain) deletion. The touchscreen pairwise discrimination task was chosen by virtue of its: (a) conceptual and technical similarities to the Cambridge Neuropsychological Test Automated Battery (CANTAB) and NIH Toolbox Cognition Battery used for testing cognitive functions in humans, (b) minimal demand on motor abilities, and (c) capability to measure many aspects of learning and memory and complex cognitive functions, including cognitive flexibility. The similarity between our mouse tasks and human cognitive assays means a high translational validity in future intervention studies using preclinical models. Our study revealed that Shank3B heterozygous mice (+/-) were slower to reach criterion in the pairwise visual discrimination task, and exhibited trends toward making more errors (first trial errors) and more correction errors than wildtype mice (+/+). Open field activity was normal in +/-, ruling out hypo- or hyperactivity as potential confounds in the touchscreen test. Sociability in the three chamber test was also normal in both +/+ and +/-. These results indicate a deficit in discrimination learning in the Shank3B model of PMS and ASD, suggesting that this mouse model is a useful preclinical tool for studying neurobiological mechanisms behind cognitive impairments in PMS and ASD. The current findings are the starting point for our future research in which we will investigate multiple domains of cognition and explore pharmacological interventions.
Databáze: OpenAIRE
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