TI - Neurabin Regulates Synaptic Plasticity . AB - PP1 is known to play a major role in the control of LTP and LTD in hippocampal CA1 neurons [36] . For example , the inhibition of PP1 abolished LTD and activated LTP [15] , [16] , [37] , [38] . Considering the interaction of neurabin with PP1 , it is reasonable to believe that neurabin is important in targeting PP1 to the dendritic spine , thereby modulating long-term plasticity . Indeed , it has been reported that neurabin is involved in synaptic plasticity in neostriatum and hippocampus [20] , [25] , [26] . Our results showed that LTP is reduced in adult hippocampal slices from neurabin KO mice . These results suggest that modulation of neurabin on the synaptic plasticity may depend on brain regions , age of animals , slice preparations , genetic manipulations or acute versus chronic lack of neurabin . Reduction of LTP in the neurabin KO mice is interesting , since PP1 is critical for the induction of LTD [38] and deletion of spinophilin selectively reduced LTD . Several mechanisms may account for the altered synaptic plasticity observed in neurabin KO mice . First , since PKA and CaMKII act in parallel in controlling synaptic incorporation of GluR1 [39] , reduced PHOSphorylation of GluR1p845 may affect activity -dependent AMPA receptor trafficking . For example , the reduction in Ser 845 PHOSphorylation seen in the neurabin KO may decrease the pool of "primed" receptors , and hence inhibit LTP . To test this idea , we studied the LTP in the presence of forskolin . We found that LTP is still impaired in neurabin KO mice , suggesting that decreased in "primed" pool of GluR1 is not the mechanism . Second , since AMPA receptor -mediated EPSC is enhanced in the KO mice , the synaptic responses may have already been saturated and thus affect the following LTP induction . If this is the case , unsaturating synaptic transmission with a prior induction of LTD should "rescue" LTP in neurabin KO mice . Indeed , we found LTP is observed by preconditioning the KO mice with LTD induction ( de-depression ) , suggesting that saturated EPSCs impair the LTP induction in neurabin KO mice . However , we have to keep in mind that de-depression is a different type of synaptic plasticity , which might utilize very different induction mechanisms from that of LTP . Third , neurabin and spinophilin co-localized in spines to a large extent [22] . Therefore , the normal LTD in neurabin KO mice may be due to the functional redundancy between these two proteins and spinophilin may compensate in some way for the lost neurabin . Fourth , neurabin-binding PP1 may not directly modulate LTP or LTD . That is , some other binding proteins other than PP1 recruited by neurabin in the dendritic spine may be involved in the modulation synaptic plasticity . Further studies are clearly needed to investigate the exact signaling pathways for neurabin-related LTP .