Figure 3

Chemogenetic chronic activation of PV⁺ neurons in the mPFC of PV:Cre male and female mice increases anxiety-like behaviors in a sex-specific manner. (Top) Experimental schematic of the timeline followed. Mice injected with the control (AAV-DIO-mCherry) or the AAV-DIO-hM3DGq virus received a daily injection of CNO over the course of 21 days. Four days after the last injection, mice were tested once daily in a behavioral test to assess various sub-domains of emotional behaviors and cognitive functions. (A–F) Behavioral endpoints measured in the OF test in control or hM3DGq mice. Female mice that underwent chronic activation of mPFC PV⁺ neurons have decreased time spent in the center of the arena, longer distance travelled near the walls, and decreased number of unsupported rearing. In males, chronic activation of mPFC PV⁺ neurons did not lead to changes in behaviors in the OF test. (G) Females that submitted to chronic activation of mPFC PV⁺ neurons displayed increased latency to eat the food in the NSF test, while no change in behavior was observed in males. (H) No effect of chronic activation of mPFC PV⁺ neurons was found in the ORT. ***p < 0.001; *p ≤ 0.05. *p = 0.057 N = 7–9 per group per sex. CNO: clozapine-N-oxide; OF: open field; ORT: object recognition test; NSF: novelty-suppressed feeding test.