Fig. 3.

The TrkB agonist 7,8-DHF promotes long-term object location memory (OLM) and object recognition memory (ORM) in Fmr1 KOs.

A, Schematic of experimental paradigm for B and C. Throughout handling and habituation, WT and KO animals were injected with saline (arrows), vehicle (open arrowheads), or either vehicle or 7,8-DHF (closed arrowheads) twice daily. One hour prior to training, animals received a final injection of vehicle or 7,8-DHF. Retention was tested 24 h later. B, Discrimination indices of 7,8-DHF-treated WTs were indistinguishable from those that received vehicle. Vehicle-treated KOs performed significantly worse than vehicle-treated WTs (F_1,32 = 2.63; Bonferroni post-test, *P < .05), but KOs that received 7,8-DHF exhibited similarly robust OLM as 7,8-DHF-treated WTs. This effect was significant when compared to mutants that received vehicle (Bonferroni post-test, *P < .05; n = 9/group). C, Exploration time (ET; circles) and distance traveled (DT; red squares) for both genotypes that received vehicle (open shapes) and 7,8-DHF (closed shapes) during training and retention trials are shown (n = 9/group). D, In animals given 7,8-DHF orally for one month prior to training, OLM discrimination indices for vehicle-treated KOs were significantly less than those for vehicle-treated WTs (F_1,36 = 10.89; Bonferroni post-test, ***P < .001), but 7,8-DHF normalized mutant performance to that of WTs (n ≥ 9/group), an effect that was significantly greater than mutants that received vehicle (Bonferroni post-test, ***P < .001). E, When vehicle or 7,8-DHF was given once one hour prior to training in experimentally-naïve animals and retention was tested one day later, vehicle-treated KOs performed significantly worse than vehicle-treated WTs (F_1,31 = 6.95; Bonferroni post-test, ***P < .001), but 7,8-DHF robustly restored their memory (Bonferroni post-test, ***P < .001; n ≥ 8/group). F, Vehicle or 7,8-DHF was again given prior to training; retention for ORM was tested one day later by changing the identity, rather than the location, of one of the objects. Vehicle-treated KOs showed an impairment in this type of memory compared to vehicle-treated WTs, though this difference was not significant (F_1,36 = 1.00; Bonferroni post-test, P > .05). 7,8-DHF robustly potentiated mutant ORM such that their discrimination indices were significantly higher than both WTs that received the compound (Bonferroni post-test, **P < .01) and KOs that received vehicle (***P < .001; n = 10/group).