Astrocytic TRPA1 as a target in reversing social avoidance by low-intensity focused ultrasound stimulation in mice

Social avoidance is a prominent clinical feature of multiple neuropsychiatric disorders. Increasing evidence showed that the medial prefrontal cortex (mPFC) regulates social avoidance with suppression of excitatory neurons. Our previous study found that the low-intensity focused ultrasound (LIFUS), as a novel noninvasive neuromodulation technique, could alleviate the social avoidance of social defeat stress (SDS) model mice by increasing the mPFC excitation. However, the underlying target of LIFUS on mPFC neurons in social defeated mice remains unclear. Here we injected AAV-shRNA to knock down astrocytic TRPA1 in the mPFC, and investigated whether astrocytic TRPA1 played a crucial role in LIFUS modulation. We found that the social avoidance of SDS mice with TRPA1 knocked down was not affected by LIFUS. Furthermore, LIFUS didn't induce enhanced expression of membrane NMDAR2A and NMDAR2B in SDS mice with TRPA1 knocked down, compared with that in mice infected with the control virus. It is believed that LIFUS can act on astrocytic TRPA1 to improve social avoidance and hence synaptic function.