Impaired long-term spatial and recognition memory and enhanced CA1 hippocampal LTP in the dystrophin-deficient Dmdmdx mouse

Abstract

Duchenne muscular dystrophy (DMD) is associated with cognitive deficits that may result from dystrophin deficiency in neurons. However, in the dystrophin-deficient Dmdmdx mouse model of DMD, the nature of the memory impairment is not well characterised and its biological substrate is uncertain. Here, we demonstrate that dystrophin deficiency in Dmdmdx mice impairs long-term, but not short-term, object recognition memory and impairs long-term spatial memory, but not acquisition, following massed training in the water maze. Furthermore, we show that the abnormal enhancement of CA1 hippocampal LTP in Dmdmdx mice is not restricted to short-lasting mechanisms, but also affects the maintenance phase of LTP of both synaptic efficacy and neuronal excitability. We conclude that dystrophin loss alters memory consolidation in both spatial and nonspatial learning tasks, at least in part due to altered synaptic plasticity mechanisms, and suggest that the severity of the deficits may depend on the nature of the training procedure.

Keywords

• Duchenne muscular dystrophy
• Cognitive impairment
• Spatial learning
• Water maze
• Object recognition
• Mutant mice