Cortico-hippocampal GluN2B is essential for efficient visual-spatial discrimination learning in a touchscreen paradigm.

Discrimination of similar spatial locations, an important feature of episodic memory, has traditionally been measured via delayed nonmatching-to-location tasks. Recently, we and others have demonstrated that touchscreen-based Trial Unique Nonmatching-to-Location (TUNL) tasks are sensitive to lesions of the dorsal hippocampus in the mouse. Previously we have shown that loss of the GluN2B subunit of the N-methyl-D-aspartate (NMDA) receptor in the dorsal CA1 and throughout the cortex impairs hippocampal-dependent water maze and fear conditioning paradigms. We investigated whether loss of GluN2B would alter performance of visual-spatial discrimination learning in a delay- or separation-dependent manner. GluN2B null mutants displayed initial impairments in accuracy on the easiest training variant of TUNL that were overcome with training. Loss of GluN2B also impaired performance on a problem series where delay and separation were systematically varied. We also observed a training-dependent effect on performance. Mutant mice that received extensive training performed similar to control mice when challenged on a variable delay and variable separation problem, while those that received minimal training were impaired across all delays and separations. Together, these data demonstrate that GluN2B in the dorsal CA1 and cortex are essential for efficient visual-spatial discrimination learning on the TUNL task. Further, training effects on performance in mutant mice suggest that alterations in synaptic plasticity after GluN2B loss may underlie intra- versus inter-session learning.