Characterization of the neural circuits revealed by maternal immune activation model (MIA) of neurodevelopmental disorders

Proprioception is a sense that inform us of our body position in space. It is detected by several kinds of proprioceptors located at joints, muscles and golgi tendon organs. Proprioceptive sensory feedback is necessary for various motor function including motor planning, learning, and adaptation. It is, thus, not surprising that patients with proprioceptive dysfunction have difficulties in various aspects of motor skills. However, where in the primary somatosensory cortex proprioceptive information is encoded and whether this information is relayed to be used as sensory feedback during motor adaption is poorly understood.

Dr. Choi and colleagues have observed that offspring prenatally exposed to maternal immune activation (MIA) display autism-associated behaviors that correlate with the presence of localized cortical lesions. More specifically, they showed that the cortical abnormalities are preferentially localized to the dysgranular zone of the primary somatosensory cortex (S1DZ) in the adult MIA offspring and that an increase in neural activity in this brain region is causal to the emergence of abnormal MIA behavioral phenotypes.

S1DZ is a region of the primary somatosensory cortex that is implicated in muscle- and joint-related proprioceptive functions. In order to understand how the activity in this particular region of the S1 is driving multiple autism-like behaviors, it will be crucial to characterize nature of sensory inputs feeding into S1DZ and how this information is used to regulate cognitive behaviors such as sociability. Thus, in this project, Dr. Choi and colleagues will 1) examine if S1DZ receives proprioceptive inputs from the periphery; 2) examine if S1DZ responds to stimulations of proprioceptive sensory neurons; 3) ask if dysregulated neural activity of proprioceptive sensory neurons is sufficient to induce MIA-associated behaviors; and 4) examine if manipulations of S1DZ neural activity impair motor adaptation and/or generalization.

A body of evidence suggests that proper processing of proprioceptive information is impaired in patients with autism. Motor dysfunction is also known to be one of the most consistent co-morbid symptoms observed in these patients. In this regard, Dr. Choi’s studies might not only reveal a novel neural substrate mediating sensory-motor transformation, but also how such a process might impact complex behaviors like social interactions.