Figure 3.

Knockdown of Nr4a2, but not Nr4a1, in cortical regions including the insular, perirhinal, and entorhinal cortices reduces preference for the novel object in the object recognition (ORM) task, while hippocampal knockdown of both Nr4a1 and Nr4a2 affects performance in the object location (OLM) task. (A) siRNA directed against Nr4a1 significantly reduced hippocampal expression of Nr4a1 (P = 0.04) without affecting Nr4a2 (P = 0.25). (B) siRNA against Nr4a2 significantly reduced hippocampal expression of Nr4a2 (P = 0.02) without affecting Nr4a1 expression (P = 0.17). (C) Forty-eight hours after infusion, habituated animals received 10 min of training with two identical objects. Another 24 h later they were given a retention test in which one object was moved to a novel location. (D) During a 24-h retention test, mice that received hippocampal infusions of either siNr4a1 or siNr4a2 displayed no preference in the OLM task in contrast to animals that received control RISC-free siRNA (P = 0.002). (E) Habituated mice received intracerebroventricular (ICV) infusions of control RISC-free, Nr4a1, or Nr4a2 siRNA. Forty-eight hours later they received 10 min of training with two identical objects. Twenty-four hours later they were given a retention test where one object was replaced with a novel object. (F) During a 24-h retention test, mice that received ICV infusions of siNr4a2 displayed no preference for the novel object in contrast to animals that received control RISC-free siRNA or siNr4Aa1 (P = 0.03). (G) Intracerebroventricular infusions of Nr4a1 siRNA did not change expression of NR4A1 in the cortex, as measured by immunohistochemistry (P = 0.4). (H) Intracerebroventricular infusions of Nr4a2 siRNA significantly decreased expression of NR4A2 in the cortex, as measured by immunohistochemistry (P = 0.02).