Auditory processing deficits in autism: auditory brainstem disturbances and the role of neuroligin-3

Project Leader: Ursula Koch e-mail


Patients with autism spectrum disorders (ASD) often display severe problems in processing acoustic information, especially complex sounds such as speech. Auditory brainstem response (ABR) recordings indicate that this impairment at least partially originates in the auditory brainstem where the temporal information of sounds is analyzed. Moreover, auditory brainstem morphology is greatly distorted in autistic people and in an animal model of ASD. In the proposed project we will investigate physiological and anatomical changes in auditory brainstem circuitry in ASD mouse models using in vitro and in vivo electrophysiological recordings. Two different ASD mouse models will be used. First, mutations of neuroligin-3 (Nlgn3), a synaptic scaffolding protein of the Neurexin-Neuroligin-Shank complex, has been associated with human autism and Nlgn3 mouse mutants or Nlgn3 knockdowns, show autistic social behavior, impaired vocalizations and modified synaptic plasticity. Second, we will expose embryos to valproic acid (VPA), which increases the risk of autism in humans and elicits autism related behavior and anatomical changes in an animal model. We will analyze synaptic and membrane properties of neurons in acute brain slices of the lateral superior olive (LSO) and the ventral nucleus of the lateral lemniscus (VNLL), two nuclei that analyze the temporal pattern of sounds. These in vitro electrophysiological experiments will be combined with immunolabelling to reveal the relative number and location of inhibitory and excitatory synapses. Finally, we will investigate sound processing deficits in the two ASD mouse models, by recording the response of single neurons in the VNLL and DNLL to simple and temporally complex sounds including mouse vocalizations. Comparing our findings in the VPA and the Nlgn3 mouse models will elucidate general and specific alterations in auditory brainstem physiology in ASD mouse models. Moreover, we will gain insight into the role of Nlgn3 for the development of specific neural circuits necessary for complex sensory processing. Finally, these experiments will help us to understand the physiological basis of auditory processing deficits in people with ASD and may help to find specific treatments for auditory processing disorder in the future.