Abstract

Fragile X syndrome (FXS) is the leading monogenetic cause of cognitive impairment and autism spectrum disorder. Area CA1 of the hippocampus receives current information about the external world from the entorhinal cortex via the temporoammonic (TA) pathway. Given its role in learning and memory, it is surprising that little is known about TA long-term potentiation (TA-LTP) in FXS. We found that TA-LTP was impaired in fmr1 KO mice. Furthermore, dendritic Ca2+ influx was smaller and dendritic spike threshold was depolarized in fmr1 KO mice. Dendritic spike threshold and TA-LTP were restored by block of A-type K+ channels. The impairment of TA-LTP coupled with enhanced Schaffer collateral LTP may contribute to spatial memory alterations in FXS. Furthermore, as both of these LTP phenotypes are attributed to changes in A-type K+ channels in FXS, our findings provide a potential therapeutic target to treat cognitive impairments in FXS.