Most individuals with autism experience at least one form of hypersensitivity from the five senses. These alterations in sensory-related behaviors can lead to profound limitations on an individual’s ability to work, interact with family and participate in leisure activities. Furthermore, these atypical responses to otherwise normal sensory stimuli may be closely associated with the core symptoms of autism, such as social deficits and repetitive behaviors. Despite the importance of sensory abnormalities in the pathogenesis of autism, how the brains of individuals with autism receive information from the five senses at the subcortical level and how such information becomes transformed into aversive responses has not been investigated.

Previous studies have shown that, when exposed to mildly aversive sensory signals, children with autism show abnormal hyperactivity in brain areas that process sensory information and emotions, as compared to typically developing children. One of these hyperactive regions is the amygdala, the brain’s emotion center that controls fear and anxiety. The amygdala is also known to integrate sensory information and emotion to maintain homeostasis against external stimuli. However, the relevance of this area for sensory hypersensitivity traits in autism has not been rigorously tested.

Sung Han plans to examine the underlying neural circuits that transmit aversive sensory signals to the amygdala. Sensory hypersensitivity could arise from hypersensitivity of amygdala neurons in response to normal sensory stimuli or, alternatively, normal amygdala neurons could receive exaggerated signals from sensory modalities. Han will focus on neuropeptide calcitonin gene-related peptide (CGRP) neurons in the pontine parabrachial nucleus (PBN), which relay multimodal sensory signals to the amygdala. Preliminary data shows that the CGRP-positive neurons relay multimodal aversive sensory information to the amygdala, across all five sensory modalities.

To test whether sensory hypersensitivity in autism arises due to exaggerated sensory signals from hypersensitive CGRP neurons to the amygdala, Han will use in vivo calcium imaging and in vivo electrophysiology to observe the PBN CGRP neuronal activity during transmission of aversive sensory signals in mouse models of autism compared to wild-type littermates. He will also manipulate the activity of the CGRP neurons in the PBN with optogenetic/chemogenetic tools during aversive sensory transmission to rescue the sensory hypersensitivity phenotype in autism mouse models. Successful completion of the proposed studies could provide fundamental circuit-level insight into the sensory hypersensitivity symptom in autism and deliver critical knowledge for developing specific therapeutic approaches to treat sensory hypersensitivity in autism.