Knockdown of the Candidate Dyslexia Susceptibility Gene Homolog Dyx1c1 in Rodents: Effects on Auditory Processing, Visual Attention, and Cortical and Thalamic Anatomy

Abstract

The current study investigated the behavioral and neuroanatomical effects of embryonic knockdown of the candidate dyslexia susceptibility gene (CDSG) homolog Dyx1c1 through RNA interference (RNAi) in rats. Specifically, we examined long-term effects on visual attention abilities in male rats, in addition to assessing rapid and complex auditory processing abilities in male and, for the first time, female rats. Our results replicated prior evidence of complex acoustic processing deficits in Dyx1c1 male rats and revealed new evidence of comparable deficits in Dyx1c1 female rats. Moreover, we found new evidence that knocking down Dyx1c1 produced orthogonal impairments in visual attention in the male subgroup. Stereological analyses of male brains from prior RNAi studies revealed that, despite consistent visible evidence of disruptions of neuronal migration (i.e., heterotopia), knockdown of Dyx1c1 did not significantly alter the cortical volume, hippocampal volume, or midsagittal area of the corpus callosum (measured in a separate cohort of like-treated Dyx1c1 male rats). Dyx1c1 transfection did, however, lead to significant changes in medial geniculate nucleus (MGN) anatomy, with a significant shift to smaller MGN neurons in Dyx1c1-transfected animals. Combined results provide important information about the impact of Dyx1c1 on behavioral functions that parallel domains known to be affected in language-impaired populations as well as information about widespread changes to the brain following early disruption of this CDSG.