Evaluation of visual motion perception ability in mice with knockout of the dyslexia candidate susceptibility gene Dcdc2

Abstract

Developmental dyslexia is a heritable disability characterized by difficulties in learning to read and write. The neurobiological and genetic mechanisms underlying dyslexia remain poorly understood; however, several dyslexia candidate risk genes have been identified. One of these candidate risk genes-doublecortin domain containing 2 (DCDC2)-has been shown to play a role in neuronal migration and cilia function. At a behavioral level, variants of DCDC2 have been associated with impairments in phonological processing, working memory and reading speed. Additionally, a specific mutation in DCDC2 has been strongly linked to deficits in motion perception-a skill subserving reading abilities. To further explore the relationship between DCDC2 and dyslexia, a genetic knockout (KO) of the rodent homolog of DCDC2 (Dcdc2) was created. Initial studies showed that Dcdc2 KOs display deficits in auditory processing and working memory. The current study was designed to evaluate the association between DCDC2 and motion perception, as these skills have not yet been assessed in the Dcdc2 KO mouse model. We developed a novel motion perception task, utilizing touchscreen technology and operant conditioning. Dcdc2 KOs displayed deficits on the Pairwise Discrimination task specifically as motion was added to visual stimuli. Following behavioral assessment, brains were histologically prepared for neuroanatomical analysis of the lateral geniculate nucleus (LGN). The cumulative distribution showed that Dcdc2 KOs exhibited more small neurons and fewer larger neurons in the LGN. Results compliment findings that DCDC2 genetic alteration results in anomalies in visual motion pathways in a subpopulation of dyslexic patients.

White matter deficits correlate with visual motion perception impairments in dyslexic carriers of the DCDC2 genetic risk variant

“…Indeed, our previous results showed that the motion deficit can be observed only at high spatial frequency, at short exposure where eye movement cannot play a role, and at low contrast: these are the stimulus characteristics where motion detectors are particularly fragile in detecting direction. Corroborating our observation in humans, murine models of the same genetic alterations show impairments in motion perception (Rendall et al 2017), together with other sensory deficits (Gabel et al 2012;Truong et al 2015;Centanni et al 2016), suggesting that dyslexics carriers of DCDC2 mutation may constitute a specific subtype of dyslexia where the sensory deficits are a distinctive feature. Given the importance of the issue, we present here evidence that the DCDC2 deletion have deficit in white matter that correlates with the motion deficit, strengthening the suggestion that dyslexia phenotypes with DCDC2 alteration may have different behavioral and brain structure and should be subclustered in the large population of poor readers.…”

“…Animal models of DCDC2 deletion have suggested that DCDC2 gene is important for neuronal migration in utero (Poelmans et al, 2011). Interestingly, Rendall et al, (2017) have demonstrated that in the DCDC2d+ KO mouse LGN neurons are smaller in size, suggesting alteration at the thalamic level. The KO mice are also impaired in motion discrimination, corroborating the influence of the DCDC2 neuronal migration in shaping early visual pathways (Rendall et al 2017).…”

“…Interestingly, Rendall et al, (2017) have demonstrated that in the DCDC2d+ KO mouse LGN neurons are smaller in size, suggesting alteration at the thalamic level. The KO mice are also impaired in motion discrimination, corroborating the influence of the DCDC2 neuronal migration in shaping early visual pathways (Rendall et al 2017). It would be important to compare FA along the optic radiation tracks between the two groups to reveal possible alteration.…”

Identifying interactive biological pathways associated with reading disability

“…Reading disability is a heritable neurodevelopmental condition with a typical age of identification between 7 and 10 years old and affects about 10% of all school‐aged children (Kamhi & Catts, 2012). Reading disability is a complex disorder affecting a number of skills and abilities, including problems with decoding (Catts, 2017), delayed and disordered phonological processing (Beitchman & Young, 1997; Clercq et al, 2017; Peter, Lancaster, Vose, Middleton, & Stoel‐Gammon, 2017), reduced language functioning (Tomblin, Zhang, Buckwalter, & Catts, 2000; Torppa, Lyytinen, Erskine, Eklund, & Lyytinen, 2010), potential deficits in working memory performance (Beneventi, Tonnessen, & Ersland, 2009; Cirino et al., 2018), and abnormal auditory and visual processing (Rendall, Perrino, LoTurco, & Fitch, 2019; Sharma, Purdy, & Kelly, 2009; Sperling, Lu, Manis, & Seidenberg, 2005). Additionally, individuals with reading disability process reading, language, auditory, and visual information differently compared to peers in neuroimaging studies (D'Mello & Gabrieli, 2018; Martin, Kronbichler, & Richlan, 2016; Martin, Schurz, Kronbichler, & Richlan, 2015).…”

“…Buckwalter, & Catts, 2000;Torppa, Lyytinen, Erskine, Eklund, & Lyytinen, 2010), potential deficits in working memory performance (Beneventi, Tonnessen, & Ersland, 2009;Cirino et al, 2018), and abnormal auditory and visual processing (Rendall, Perrino, LoTurco, & Fitch, 2019;Sharma, Purdy, & Kelly, 2009;Sperling, Lu, Manis, & Seidenberg, 2005). Additionally, individuals with reading disability process reading, language, auditory, and visual information differently compared to peers in neuroimaging studies (D'Mello & Gabrieli, 2018;Martin, Kronbichler, & Richlan, 2016;Martin, Schurz, Kronbichler, & Richlan, 2015).…”