CREB transcription in the medial prefrontal cortex regulates the formation of long-term associative recognition memory

Blockade of CREB function in the medial prefrontal cortex (mPFC) impaired long-term but not short-term associative recognition memory formation and did not alter long-term nonassociative recognition memory formation. (A) Blockade of CREB function in the mPFC impaired long-term, but not short-term object-in-place memory. T-tests comparing the DRs of each group against chance performance revealed that at the 5 min and 3 h delays, both the EGFP and A-CREB groups showed significant object-in-place discrimination [5 min EGFP t₍₉₎ = 7.08, P = 0.0001, A-CREB t₍₉₎ = 12.95, P = 0.0001; 3 h EGFP t₍₉₎ = 6.11, P = 0.0001, A-CREB t₍₉₎ = 10.87, P = 0.0001]. In contrast at the 6 and 24 h delay the EGFP group showed significant discrimination [6 h t₍₉₎ 9.50, P = 0.0001; 24 h t₍₉₎ = 7.131, P = 0.0001] whereas the A-CREB group did not [6 h t₍₉₎ = −0.13 P = 0.899; 24 h t₍₉₎ = 0.30, P = 0.77]. (B) Blockade of CREB function in the mPFC impaired long-term, but not short-term temporal order memory. T-tests comparing the DRs of each group against chance performance revealed that at the 3 h delay both the EGFP and A-CREB groups showed significant discrimination between the object presented in S2 and S3 [EGFP t₍₉₎ = 4.09, P = 0.003; A-CREB t₍₉₎ = 5.25, P = 0.001]. At the 6 h delay the EGFP group showed significant discrimination [t₍₉₎ = 3.27, P = 0.010] while the A-CREB did not show significant discrimination [t₍₉₎ = −0.91, P = 0.385]. (C) Blockade of CREB function in the mPFC impaired long-term, but not short-term temporal location memory. T-tests comparing the DRs of each group against chance performance revealed that at the 3 h delay both the EGFP and A-CREB groups showed significant discrimination between the object presented in S2 and S3 [EGFP t₍₉₎ = 3.54, P = 0.006; A-CREB t₍₉₎ = 9.24, P = 0.000]. At the 6 h delay the EGFP group showed significant discrimination [t₍₉₎ = 5.62, P = 0.000] while the A-CREB did not show significant discrimination [t₍₉₎ = −0.12, P = 0.91]. (D) Blockade of CREB function in the mPFC had no effect on novel object recognition or object location memory. T-tests comparing the DRs against chance performance revealed that all groups showed significant discrimination between the novel and familiar objects in the object recognition task [EGFP t₍₉₎ = 8.060, P = 0.000; A-CREB t₍₉₎ = 5.61, P = 0.000]. Both groups also showed significant discrimination between the moved and unmoved objects in the object location task [EGFP t₍₉₎ = 4.23, P = 0.002; A-CREB t₍₉₎ = 7.00, P = 0.000]. Data presented as mean ± SEM. (***) P < 0.001.