Intact spatial learning in Fmr1–/y, Syngap1+/–, and Grin2b+/– rat models of neurodevelopmental disorders

Abstract

FMR1, SYNGAP1, and GRIN2B gene mutations Q8 are known causes of mild to severe intellectual disability (ID) in humans, with affected individuals frequently co-diagnosed with autism spectrum disorder (ASD). These three genes influence molecular mechanisms underlying synaptic plasticity, and thus spatial memory behaviors have been of interest in studying rodent models of these mutations. However, evidence of spatial memory impairment across these models is inconsistent, with some studies reporting deficits and others finding none. In the present study, we used a variant of the Morris water maze that allowed explicit stimulus control of visual landmarks and examined the use of individual visual cues to navigate, using Fmr1 –/y , Syngap1 +/– , and Grin2b +/– rat models. We found 1) strong landmark control of spatial behavior and 2) intact learning in all three rat models. Of general significance, our results also suggest that rats use a spatial strategy that relies on individual landmarks (at least in a directional water maze), as opposed to the configuration of landmarks, to identify the goal location.