Figure 2

Injection of an AAV-DIO-hM3DGq DREADD virus in the mPFC of PV:Cre mice. (A) Representative coronal image shows bilateral expression of mCherry localized to the infralimbic cortex (IL) and part of the prelimbic cortex (PrL). Scale bar: 50 µm. (B) Representative images showing selective expression of the hM3DGq virus (red) in parvalbumin (PV – green) interneurons. Scale bar: 20 µm. (C) Stereological analysis indicated that 92.23 ± 1.31% of mPFC PV⁺ neurons expressed the control or hM3DGq virus, and (D) 96.85 ± 0.70% mCherry cells are PV⁺. (E) Verification of hM3DGq virus response to acute and chronic (once per day for 21 days) CNO injection using stereological analysis of the number of mCherry cells expressing cFos: both acute and chronic injection of CNO in the PFC of mice expressing the hM3DGq virus leads to high expression of cFos in mCherry cells when compared to cells expressing the control virus. Representative image of mCherry cells expressing cFos (white arrow) vs. mCherry cells not expressing cFos (white arrowhead). Scale bar: 20 µm. (F) Verification that acute and chronic chemogenetic activation of prefrontal PV⁺ cells lead to hypofunction of the PFC: both regimen of CNO injection reduce significantly the amount of cFos⁺ cells, showing overall hypofrontality. Representative images of cFos expression in the PFC of mice expressing the control or the hM3DGq virus. Scale bar: 20 µm. **p < 0.001; ***p < 0.0001.