Auditory cue perception in the Cntnap2 rat model of autism

• Applicant: Dr. Dorit Möhrle
• Subject Area: Biological Psychiatry ; Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry ; Cognitive, Systems and Behavioural Neurobiology
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 442662585

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders estimated to affect 1 in 59 children. The key symptoms of ASD - deficits in social communication and language acquisition - have been proposed to be a consequence of inaccurate sound processing during development of the auditory system. In children with ASD, the neural encoding of complex sounds with rapidly changing temporal features such as speech has been shown to be instable. This deficit is probably due to aberrant activity in the Inferior Colliculus in the auditory midbrain and imbalanced neuronal excitation/inhibition in prefrontal brain regions. Rapid auditory speech processing is developmentally regulated by one of the susceptibility genes of ASD, the contactin associated protein-like 2 (CNTNAP2), both in clinical and general populations. Mice and rats lacking Cntnap2 show core deficits of human ASD, e.g. in social communication, auditory processing, cortical neuronal synchrony and activity in the prefrontal cortex. However, the neural basis of the ASD-related auditory impairments is still not fully understood. I propose to examine how physiological underpinnings of sound processing acuity in auditory pathways change with varying levels of ASD traits and to test the influence of prefrontal brain activity. I will take a translational approach to study neural encoding precision in relation to perceptual sound judgement correlated to ASD traits in rats and humans. The proposed project is a multi‐site collaboration involving four labs at the University of Western Ontario. The proposed research has three aims: (1) to elucidate alterations in encoding precision in the auditory pathway and activity in prefrontal areas that explain impaired sound discrimination abilities in Cntnap2 knockout compared to wild-type rats, (2) to relate deficits in neural encoding precision to anatomical changes in selected auditory nuclei and prefrontal areas, and (3) establish a translational approach in humans. The proposed experiments will uncover the changes in auditory processing that might present fundamental mechanisms of speech processing deficits associated with ASD. Although only a minor percentage of the autistic population harbor deletions of CNTNAP2, knowledge of the altered auditory pathway physiology related with autistic traits might help to develop objective neural markers. Such markers could facilitate to predict if infants are at risk for ASD and to identify improved therapies for the many individuals suffering from speech processing disruptions associated with ASD.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Hosts: Professor Dr. Brain Allman; Professorin Dr. Susanne Schmid
• Participating Persons: Dr. Björn Herrmann; Dr. Ryan Stevenson