Auditory cue perception in the Cntnap2 rat model of autism
Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
Cognitive, Systems and Behavioural Neurobiology
Final Report Abstract
To fully develop, our brains must undergo an enormous amount of intricate and timely development within a short period of time. Unfortunately, this leaves the brain extremely vulnerable to any changes that occur during this sensitive period. Alterations in brain development can lead to neurodevelopmental disorders such as Autism Spectrum Disorders (ASD). ASD are complex, pervasive developmental disorders, that are that are estimated to affect 1 in 59 children. ASD is often accompanied by hearing difficulties - estimates based on caretaker reports suggest up to 80%. Auditory hypersensitivity, a condition in which everyday sounds are perceived as much louder than normal, is a prominent symptom in ASD and may contribute to other phenotypes such as social difficulties. Many of these hearing difficulties result from alterations in brain-related processing of sound, i.e. how the brain makes sense of sound detected by the ears. Therapeutic interventions for ASD can improve the lives of affected individuals and their families. However, to date, there are no treatments that specifically address the underlying brain alterations. The present study utilized a well-established genetic rodent model of autism with a mutation in the gene contactin-associated protein-like 2 (Cntnap2) gene. CNTNAP2 was first identified in an Old Order Amish population who show high prevalence of severe ASD. The investigatory drug R-Baclofen improved auditory hypersensitivity and poorer sound discrimination abilities in rats with mutation in the Cntnap2 gene. Social deficits in later life of rats with Cntnap2 mutation could be ameliorated by intervening with environmental factors during the early phase of development. Finally, imaging techniques revealed changes in brain chemistry in brain regions involved in auditory processing and social behavior in rats with Cntnap2 mutation. The outcomes of this project help to fill gaps in our knowledge on how people with ASD perceive and process sounds. We learned more about the underlying cellular changes in brain areas that are essential for decoding these sounds and also for social interactions. These findings could help pave the way for the development of effective treatments to improve auditory processing and social difficulties in ASD.
Publications
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Characterizing ultrasonic vocalization in a gene-environment interaction model for autism. International Behavioral Neuroscience Society, Virtual
Möhrle D., Yuen P.M., Zheng A., Haddad F. & Schmid S.
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GABAB receptor agonist R-Baclofen reverses altered auditory reactivity and filtering in the Cntnap2 knock-out rat model for neurodevelopmental disorders. International Society for Autism Research, Virtual
Möhrle D., Wang W., Whitehead S.N. & Schmid S.
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GABAB Receptor Agonist R-Baclofen Reverses Altered Auditory Reactivity and Filtering in the Cntnap2 Knock-Out Rat. Frontiers in Integrative Neuroscience, 15.
Möhrle, Dorit; Wang, Wenxuan; Whitehead, Shawn N. & Schmid, Susanne
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Reversal of altered auditory reactivity and filtering in the Cntnap2 knock-out rat model for autism by selective activation of GABAB receptors with R-Baclofen. Göttingen Meeting of the German Neuroscience Society, Virtual
Möhrle D., Wang W., Whitehead S. & Schmid S.
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Selective activation of GABAB receptors reverses altered auditory reactivity and sensory filtering in the Cntnap2 knock-out rat model for Autism. Neuroscience Research Day, Virtual
Möhrle D., Wang W., Whitehead S.N. & Schmid S.
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Characterizing maternal isolation-induced ultrasonic vocalizations in a gene-environment interaction rat model for autism. Neuroscience Research Day, Virtual
Möhrle D., Yuen P.M.M., Zheng A., Haddad F., Allman B.L. & Schmid S.
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Gene-environment interactions alter postnatal vocal communication, juvenile play and adult social behavior in a rat model for autism. Annual Dr. Benjamin Goldberg Developmental Disabilities Research Day, Virtual
Möhrle D., Doornaert E., Yuen P.M.M., Zheng A., Allman B.L & Schmid S.
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Gene-environment interactions exacerbate altered ultrasonic vocalization syntax in a rat model for neurodevelopmental disorders. Canadian Neuroscience Meeting, Toronto, Ontario
Möhrle D., Yuen P.M.M, Zheng A., Haddad F., Allman B.L. & Schmid S.
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Interaction of ASD risk gene mutation and parental environment alters early vocal communication and social behavior in the Cntnap2 knockout rat model. Joint Neuroscience Conference & CPIN Research Day, Virtual
Möhrle D., Doornaert E., Yuen P.M.M., Zheng A., Allman B.L & Schmid S.
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Assessing the Cntnap2 knockout rat prepulse inhibition deficit through prepulse scaling of the baseline startle response curve. Translational Psychiatry, 13(1).
El-Cheikh, Mohamad Alaa; Möhrle, Dorit; Haddad, Faraj L.; Rose, Anton; Allman, Brian L. & Schmid, Susanne
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Characterizing maternal isolation‐induced ultrasonic vocalizations in a gene–environment interaction rat model for autism. Genes, Brain and Behavior, 22(3).
Möhrle, Dorit; Yuen, Megan; Zheng, Alice; Haddad, Faraj L.; Allman, Brian L. & Schmid, Susanne
