SCSB Lunch Series: Yeong Shin Yim, Ph.D.

Date: Friday, February 3, 2017
Time: 12:00pm – 1:00pm
Speaker: Yeong Shin Yim, Ph.D.
Affiliation: Simons Center Postdoctoral Fellow, Gloria Choi Laboratory, McGovern Institute for Brain Research, MIT

Talk Title: Reversing autism-like behaviors in mouse offspring exposed to maternal inflammation
Abstract: Viral infection during pregnancy has been correlated with increased frequency of autism spectrum disorder (ASD) in offspring. This phenomenon has been modeled in mice prenatally subjected to maternal immune activation (MIA). We previously showed that the T helper 17 (Th17) cell/interleukin-17a (IL-17a) pathway is crucial for the induction of both cortical and behavioral abnormalities observed in MIA-affected offspring. However, it remains unclear if and how cortical abnormalities serve as causative factors for the aberrant behavioral phenotypes. Here, we show that cortical abnormalities are preferentially localized to a region encompassing the dysgranular zone of the primary somatosensory cortex (S1DZ) in the adult MIA offspring and that the presence and size of cortical patches tightly correlate with manifestation and severity of ASD-like behavioral phenotypes. More specifically, we demonstrate that the selective loss of parvalbumin (PV)-expressing interneurons and a concomitant increase in neural activity is causal to the emergence of MIA behavioral phenotypes. Indeed, activation of pyramidal neurons in the S1DZ was sufficient to induce ASD-like behaviors in wild-type (WT) animals, while reduction in neural activity in this cortical region rescued the behavioral abnormalities in the MIA offspring. Furthermore, we identified the temporal association area (TeA) as a S1DZ downstream target involved in the selective modulation of sociability phenotypes, but not the expression of repetitive behaviors. Our work identifies a cortical region primarily, if not exclusively, centered on the S1DZ as the major node of a neural network whose increased neural activity mediates ASD-like behavioral abnormalities observed in offspring exposed to maternal inflammation.