Mbnl2 loss alters novel context processing and impairs object recognition memory.

Patients with myotonic dystrophy type I (DM1) demonstrate visuospatial dysfunction and impaired performance in tasks requiring recognition or memory of figures and objects. In DM1, CUG expansion RNAs inactivate the muscleblind-like (MBNL) proteins. We show that constitutive Mbnl2 inactivation in mice selectively impairs object recognition memory in the novel object recognition test. When exploring the context of a novel arena in which the objects are later encountered, the dorsal hippocampus responds with a lack of enrichment for learning and memory-related pathways, mounting instead transcriptome alterations predicted to impair growth and neuron viability. In mice, saturation effects may prevent deployment of a functionally relevant transcriptome response during novel context exploration. Post-novel context exploration alterations in genes implicated in tauopathy and dementia are observed in the dorsal hippocampus. Thus, MBNL2 inactivation in patients with DM1 may alter novel context processing in the dorsal hippocampus and impair object recognition memory.