title: Cognitive dysfunction in the dystrophin-deficient mouse model of Duchenne muscular dystrophy: A reappraisal from sensory to executive processes.
abstract: Duchenne muscular dystrophy (DMD) is associated with language disabilities and deficits in learning and memory, leading to intellectual disability in a patient subpopulation. Recent studies suggest the presence of broader deficits affecting information processing, short-term memory and executive functions. While the absence of the full-length dystrophin (Dp427) is a common feature in all patients, variable mutation profiles may additionally alter distinct dystrophin-gene products encoded by separate promoters. However, the nature of the cognitive dysfunctions specifically associated with the loss of distinct brain dystrophins is unclear. Here we show that the loss of the full-length brain dystrophin in mdx mice does not modify the perception and sensorimotor gating of auditory inputs, as assessed using auditory brainstem recordings and prepulse inhibition of startle reflex. In contrast, both acquisition and long-term retention of cued and trace fear memories were impaired in mdx mice, suggesting alteration in a functional circuit including the amygdala. Spatial learning in the water maze revealed reduced path efficiency, suggesting qualitative alteration in mdx mice learning strategy. However, spatial working memory performance and cognitive flexibility challenged in various behavioral paradigms in water and radial-arm mazes were unimpaired. The full-length brain dystrophin therefore appears to play a role during acquisition of associative learning as well as in general processes involved in memory consolidation, but no overt involvement in working memory and/or executive functions could be demonstrated in spatial learning tasks.
authors.affiliation: Paris-Saclay Neuroscience Institute, UMR 9197, CNRS, F-91405 Orsay, France; Univ. Paris-Sud, UMR 9197, F-91405 Orsay, France; Université Paris-Saclay, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Chaussenot
authors.affiliation: Paris-Saclay Neuroscience Institute, UMR 9197, CNRS, F-91405 Orsay, France; Univ. Paris-Sud, UMR 9197, F-91405 Orsay, France; Université Paris-Saclay, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Edeline
authors.affiliation: Paris-Saclay Neuroscience Institute, UMR 9197, CNRS, F-91405 Orsay, France; Univ. Paris-Sud, UMR 9197, F-91405 Orsay, France; Université Paris-Saclay, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Le Bec
authors.affiliation: Paris-Saclay Neuroscience Institute, UMR 9197, CNRS, F-91405 Orsay, France; Univ. Paris-Sud, UMR 9197, F-91405 Orsay, France; Université Paris-Saclay, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: El Massioui
authors.affiliation: Paris-Saclay Neuroscience Institute, UMR 9197, CNRS, F-91405 Orsay, France; Univ. Paris-Sud, UMR 9197, F-91405 Orsay, France; Université Paris-Saclay, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Laroche
authors.affiliation: Paris-Saclay Neuroscience Institute, UMR 9197, CNRS, F-91405 Orsay, France; Univ. Paris-Sud, UMR 9197, F-91405 Orsay, France; Université Paris-Saclay, France. Electronic address: cyrille.vaillend@u-psud.fr.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Vaillend
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001307:Auditory Perception / Q000502:physiology*; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D003072:Cognition Disorders / Q000235:genetics* / Q000503:physiopathology*; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem; D056344:Executive Function / Q000502:physiology; D005239:Fear / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D057567:Memory, Long-Term / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology*; D013216:Reflex, Startle; D055139:Sensory Gating / Q000502:physiology*; D065852:Spatial Memory / Q000502:physiology; D065854:Spatial Navigation / Q000502:physiology
chemical_list: D016189:Dystrophin
keywords: Associative learning; Executive functions; Hearing; Spatial learning; Working memory; mdx mouse