TI - Rescue of Hippocampal LTP in Neurabin KO Mice by Pre-conditioning with LTD Induction . AB - At least two mechanisms may underlie the loss of LTP observed in neurabin KO mice . First , the reduced PHOSphorylation of GluR1p845 in the neurabin KO may affect activity -dependent AMPA receptor contribution to LTP . Second , the synaptic responses may be saturated and simply could not undergo activity -dependent potentiation . To test the first idea , we examined whether forskolin , an adenylyl cyclase activator , could rescue the loss of LTP by increasing PKA activities and therefore PHOSphorylation of GluR1 at Ser845 site . Perfusion of forskolin ( 10 uM ) for 10 minutes significantly increased AMPA EPSCs in hippocampal CA1 neurons in wild-type mice ( 1809+-206 % of control ; n = 5 , P lt 005 , paired t-test ) ( Fig S2 ) . Similar increase was also observed in neurabin KO mice ( 1685+-215 % of control ; n = 5 , P gt 005 compared with wild-type mice , unpaired t-test ) . LTP induced by the pairing protocol was then studied in the presence of forskolin in both groups ( Fig 5A ) . We found that LTP could be observed in wild-type mice ( 1359+-100 % of baseline response , n = 7 , P gt 005 compared with control LTP , unpaired t-test ) . However , LTP is still significantly impaired in the neurabin KO mice in the presence of forskolin ( 980+-94 % of baseline response , n = 8 , P lt 005 compared with wild-type , unpaired t-test ) ( Fig 5A ) . Therefore , increasing cAMP-PKA activity could not rescue the loss of LTP in neurabin KO mice . Next , we examined whether pre-conditioning with LTD induction could rescue following LTP induction in neurabin KO mice . Similar to Fig. 2C and D , LTD could be observed in both wild-type ( 583+-50 % of baseline response , n = 5 ) and neurabin KO mice ( 688+-56 % of baseline response , n = 9 ) 10 minutes after induction ( Fig 5B ) . More importantly , we found that the LTP is observed in neurabin KO mice with pre-LTD conditioning ( 1546+-191 % of baseline response , n = 9 ) . The magnitude of potentiation is similar to that in wild-type mice ( 1464+-198 % of baseline response , n = 5 , P gt 005 , unpaired t-test ) ( Fig 5B ) . Therefore , preconditioning with LTD induction could rescue the loss of LTP in the neurabin KO mice .