Spaced training improves learning in Ts65Dn and Ube3a mouse models of intellectual disabilities

J. C. Lauterborn, M. N. Schultz, A. A. Le, M. Amani, A. E. Friedman, P. T. Leach, C. M. Gall, G. S. Lynch, Jacqueline Crawley

Research output: Contribution to journalArticle

Abstract

Benefits of distributed learning strategies have been extensively described in the human literature, but minimally investigated in intellectual disability syndromes. We tested the hypothesis that training trials spaced apart in time could improve learning in two distinct genetic mouse models of neurodevelopmental disorders characterized by intellectual impairments. As compared to training with massed trials, spaced training significantly improved learning in both the Ts65Dn trisomy mouse model of Down syndrome and the maternally inherited Ube3a mutant mouse model of Angelman syndrome. Spacing the training trials at 1 h intervals accelerated acquisition of three cognitive tasks by Ts65Dn mice: (1) object location memory, (2) novel object recognition, (3) water maze spatial learning. Further, (4) spaced training improved water maze spatial learning by Ube3a mice. In contrast, (5) cerebellar-mediated rotarod motor learning was not improved by spaced training. Corroborations in three assays, conducted in two model systems, replicated within and across two laboratories, confirm the strength of the findings. Our results indicate strong translational relevance of a behavioral intervention strategy for improving the standard of care in treating the learning difficulties that are characteristic and clinically intractable features of many neurodevelopmental disorders.

Original languageEnglish (US)
Article number166
JournalTranslational Psychiatry
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Intellectual Disability
Learning
Maze Learning
Angelman Syndrome
Water
Genetic Models
Trisomy
Standard of Care
Down Syndrome
Spatial Learning
Neurodevelopmental Disorders

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Spaced training improves learning in Ts65Dn and Ube3a mouse models of intellectual disabilities. / Lauterborn, J. C.; Schultz, M. N.; Le, A. A.; Amani, M.; Friedman, A. E.; Leach, P. T.; Gall, C. M.; Lynch, G. S.; Crawley, Jacqueline.

In: Translational Psychiatry, Vol. 9, No. 1, 166, 01.12.2019.

Research output: Contribution to journalArticle

Lauterborn, JC, Schultz, MN, Le, AA, Amani, M, Friedman, AE, Leach, PT, Gall, CM, Lynch, GS & Crawley, J 2019, 'Spaced training improves learning in Ts65Dn and Ube3a mouse models of intellectual disabilities', Translational Psychiatry, vol. 9, no. 1, 166. https://doi.org/10.1038/s41398-019-0495-5
Lauterborn, J. C. ; Schultz, M. N. ; Le, A. A. ; Amani, M. ; Friedman, A. E. ; Leach, P. T. ; Gall, C. M. ; Lynch, G. S. ; Crawley, Jacqueline. / Spaced training improves learning in Ts65Dn and Ube3a mouse models of intellectual disabilities. In: Translational Psychiatry. 2019 ; Vol. 9, No. 1.
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