Inhibition of TRPV4 rescues impaired excitability and social deficits in NAc-specific Shank3-deficient mice.

We used AAV transfection of Shank3 shRNA to study the effect of Shank3 knock down in Nucleus Accumbens neurons. We find that Shank3 knock down leads to social deficits and hyperexcitability of Nucleus Accumbens D1-MSN. Bulk RNA sequencing shows that D1-MSN with Shank3 knock down upregulate TRPV4 and its subsequent antagonist driven inhibition leads to both a rescue of D1-MSN hyperexcitability and social deficit. Analysis of Nucleus accumbens cells from experiments involving the controls AAV-Scrambled or the AAV-Shank3-Sh Virus isolating in each case 4 different types of samples: Drd1 expressing infected cells, Drd1 expressing non-infected cells, non-Drd1 expressing infected cells and non-Drd1 expressing non-infected cells.