Abstract
Rapidly approaching objects indicating threats can induce defensive response through activating a subcortical pathway comprising superior colliculus (SC), lateral posterior nucleus (LP), and basolateral amygdala (BLA). Abnormal defensive response has been reported in autism, and impaired synaptic connections could be the underlying mechanism. Whether the SC-LP-BLA pathway processes looming stimuli abnormally in autism is not clear. Here, we found that looming-evoked defensive response is impaired in a subgroup of the valproic acid (VPA) mouse model of autism. By combining the conventional neurotracer and transneuronal rabies virus tracing techniques, we demonstrated that synaptic connections in the SC-LP-BLA pathway were abnormal in VPA mice whose looming-evoked defensive responses were absent. Importantly, we further translated the finding to children with autism and observed that they did not present looming-evoked defensive response. Furthermore, the findings of the DTI with the probabilistic tractography showed that the structural connections of SC-pulvinar-amygdala in autism children were weak. The pulvinar is parallel to the LP in a mouse. Because looming-evoked defensive response is innate in humans and emerges much earlier than do social and language functions, the absence of defensive response could be an earlier sign of autism in children.
Highlights
Approaching objects, known as visual looming, constitute an intrinsic and unconditional warning cue to elicit automatic defensive response in dealing with emergency situations
An autism-like mouse model was created by exposing mice to valproic acid (VPA) on the 10.5th day of gestation, whereas mice in the control group were treated with saline (Fig. 1a)
Looming-evoked defensive responses were tested with a behavioral assay of a rapidly expanding dark disk stimulus presented overhead 15 times over 10.75 s (Fig. 1c)[5,9,10]
Summary
Known as visual looming, constitute an intrinsic and unconditional warning cue to elicit automatic defensive response in dealing with emergency situations. That is in agreement with neuroimaging studies in healthy human subjects report co-activation of subcortical structures of the amygdala, the SC, and the pulvinar nucleus of the thalamus during non-conscious visual perception of fearful stimuli[11,12,13,14]. This study aims to investigate the subcortical visual pathway, SC-LP-BLA in autism mouse model and SC-pulvinar-amygdala in children with ASD, on modulating looming induced defensive response by combining data from hypothesis-driven animal experiments with tractography data from an association study on a group of children with ASD. Translating our findings from animals to human clinical situations, we are able to provide evidence that the amygdala subcortical pathway is impaired in individuals with ASD, and it could be the underlying mechanism for their deficits in looming induced fear processing and defensive response
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