Date of Completion

7-31-2017

Embargo Period

7-31-2017

Keywords

Autism, dyslexia, language, mouse models, genetics, neuroscience

Major Advisor

Dr. R. Holly Fitch

Associate Advisor

Dr. John Salamone

Associate Advisor

Dr. Inge-Marie Eigsti

Associate Advisor

Dr. Heather Read

Associate Advisor

Dr. Joseph LoTurco

Field of Study

Psychology

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Language encompasses an ability to acquire and integrate complex cognitive systems in order to communicate with others, and inherited factors are thought to play a key role in modulating these emergent skills. In recent years, the role of genetics in language has gained focus and attention, based on accumulating empirical knowledge about the genes, proteins, and cellular machinery involved. In particular, disruption to various mechanisms has been shown to relate to impairments in language -- as seen in neurodevelopmental disorders such as autism, dyslexia and SLI. Mouse models can serve as a useful tool in studying the genetic modulators of related neural circuitry. The central over-arching aim of the current series of studies was to examine behavioral and neuroanatomic profiles of transgenic mice modeled on several established neurodevelopmental disorders (NDDs). We focused on five transgenic murine preparations exhibiting mutations derived from NDD populations characterized by atypical language. These include NDDs with language disability as a core feature of the disorder (e.g., specific language impairment (SLI), dyslexia), or as a sub-type (i.e., only some individuals affected; autism spectrum disorders (ASD)). The transgenic models assessed include: (1) Cntnap2 knock-out (KO; implicated in ASD and SLI); (2) Dyx1c1 conditional forebrain KO (implicated in dyslexia); (3) Ts2-neo model (a mutation associated with ASD); (4) Dcdc2 KO (implicated in dyslexia); and (5) Shank3b KO (associated with ASD). Using these models, we assessed specific links between: (a) genetically driven alterations in neurodevelopment; and (b) anomalies in fundamental non-verbal behaviors subserving aspects of language-learning. Our novel behavioral paradigms were able to tap “intermediate” language-related behavioral phenotypes in mice.

Amanda Rose Rendall – University of Connecticut, 2017

Measures included acoustic processing of rapid and complex stimuli, visual motion perception, sensorimotor functions, social/communicative interactions, and working memory. We also quantified gross neuroanatomy to assess whether neural anomalies correlate with any atypical behaviors. Cumulative findings provide insight about the role of genes critical in the polygenic developmental cascade supporting emergent language, as well as the consequences of disruption to those pathways. Ongoing research may promote enhanced early screening of infants, as well as individualized treatment techniques for neurodevelopmental disorders that include language and communicative impairments.

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