Brain and behaviour phenotyping of a mouse model of neurofibromatosis type-1: an MRI/DTI study on social cognition.
Neurofibromatosis type-1 (NF1) is a common neurogenetic disorder and an important cause of intellectual disability. Brain-behaviour associations can be examined in vivo using morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to study brain structure. Here, we studied structural and behavioural phenotypes in heterozygous Nf1 mice (Nf1(+/-) ) using T2-weighted imaging MRI and DTI, with a focus on social recognition deficits. We found that Nf1(+/-) mice have larger volumes than wild-type (WT) mice in regions of interest involved in social cognition, the prefrontal cortex (PFC) and the caudate-putamen (CPu). Higher diffusivity was found across a distributed network of cortical and subcortical brain regions, within and beyond these regions. Significant differences were observed for the social recognition test. Most importantly, significant structure-function correlations were identified concerning social recognition performance and PFC volumes in Nf1(+/-) mice. Analyses of spatial learning corroborated the previously known deficits in the mutant mice, as corroborated by platform crossings, training quadrant time and average proximity measures. Moreover, linear discriminant analysis of spatial performance identified 2 separate sub-groups in Nf1(+/-) mice. A significant correlation between quadrant time and CPu volumes was found specifically for the sub-group of Nf1(+/-) mice with lower spatial learning performance, suggesting additional evidence for reorganization of this region. We found strong evidence that social and spatial cognition deficits can be associated with PFC/CPu structural changes and reorganization in NF1.
Institute of Nuclear Science Applied to Health, University of Coimbra, Coimbra, Portugal.|Center for Neuroscience and Cell Biology - Institute of Biomedical Imaging and Life Science (CNC.IBILI), University of Coimbra, Coimbra, Portugal.
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Petrella
Department of Neurobiology, University of California, Los Angeles, CA, USA.|Department of Psychology, University of California, Los Angeles, CA, USA.|Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.|Integrative Center for Learning and Memory, University of California, Los Angeles, CA, USA.|Brain Research Institute, University of California, Los Angeles, CA, USA.
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Cai
Institute of Nuclear Science Applied to Health, University of Coimbra, Coimbra, Portugal.|Center for Neuroscience and Cell Biology - Institute of Biomedical Imaging and Life Science (CNC.IBILI), University of Coimbra, Coimbra, Portugal.
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Sereno
Institute of Nuclear Science Applied to Health, University of Coimbra, Coimbra, Portugal.|Center for Neuroscience and Cell Biology - Institute of Biomedical Imaging and Life Science (CNC.IBILI), University of Coimbra, Coimbra, Portugal.
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Gonçalves
Department of Neurobiology, University of California, Los Angeles, CA, USA.|Department of Psychology, University of California, Los Angeles, CA, USA.|Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.|Integrative Center for Learning and Memory, University of California, Los Angeles, CA, USA.|Brain Research Institute, University of California, Los Angeles, CA, USA.
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Silva
Institute of Nuclear Science Applied to Health, University of Coimbra, Coimbra, Portugal. mcbranco@fmed.uc.pt.|Center for Neuroscience and Cell Biology - Institute of Biomedical Imaging and Life Science (CNC.IBILI), University of Coimbra, Coimbra, Portugal. mcbranco@fmed.uc.pt.
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Castelo-Branco
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D005260:Female; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009456:Neurofibromatosis 1 / Q000000981:diagnostic imaging / Q000503:physiopathology*; D010641:Phenotype; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D012919:Social Behavior; D012920:Social Behavior Disorders / Q000503:physiopathology; D013329:Structure-Activity Relationship
Brain; magnetic resonance imaging; mice; neurofibromatosis type-1; social cognition; spatial learning