Defensive Response to Whisker Stimulation and Reduced Somatosensory Cortex Activation in the Engrailed-2 Mouse Model of Autism
Increased responsiveness to somatosensory stimuli is a common symptom in autism spectrum disorders (ASDs), which often leads to defensive behaviors in response to tactile stimulation. Recent studies performed in mouse models of ASDs confirm these findings. As an example, Fmr1 knock-out (KO) mice (a model of syndromic autism) present a marked adaptation deficit of somatosensory cortex neurons in response to repetitive whisker stimulation, which is not observed in wild-type (WT) controls.
Here we evaluated the behavioral response to whisker stimulation in Engrailed-2 (En2) KO mice, another model of ASDs characterized by a significatly reduced expression of Fmr1.
Ten WT and 10 En2 KO mice of both sexes were assessed for whisker-guided, somatosensory functions using the sensory maze exploration and whisker nuisance test. The two tests were performed in sequence on the same groups of animals. At the end of the whisker nuisance test, brains were dissected and processed for c-Fos immunohistochemistry as a marker of neuronal activity.
When tested in the sensory maze, adult En2 KO mice spent a comparable whisker-guided exploration time as their WT controls, thus indicating that whisker-mediated exploratory behavior is preserved in these mutants. Conversely, En2 KO mice showed aggressive and active avoidance responses to repeated whisker stimulation in the whisker nuisance test, which instead resulted innocuous to WT controls. Quantitative analysis of c-Fos immunohistochemistry showed that in En2 KO mice, avoidance behavior to whisker stimulation was paralleled by a significantly lower number of c-Fos positive neurons in layer IV of the primary somatosensory cortex, as compared to WT controls.
These results suggest that tactile defensiveness is accompanied by a reduced activation of somatosensory cortical circuits in En2 KO mice. Thus, impaired signal processing in the somatosensory cortex seems to be a common feature in different mouse models of ASDs, and might be a cause of tactile defensiveness in ASDs.