Figure 3.

Ca_V1.2^Tg+; Syn^Tg+ mice exhibit deficits in memory consolidation of fearful contexts. (A₁) Mice were exposed to a single tone-shock pairing each day for 3 days and subsequently returned to the same context 24 hours later, and freezing was measured in the absence of tone or shock. While all groups exhibited an increase in freezing across the 3 days of training, the Ca_V1.2^Tg+; Syn^Tg+ mice exhibited less freezing 24 hours after the first training session (day 2), a deficit which persisted across 3 days of training and was maintained during a context test on the fourth day (effect of training: F_2.638,172.9 = 197.0, p < .0001; effect of genotype: F_2,73 = 20.42, p < .0001; training × genotype interaction: F_6,219 = 3.194, p = .005; post hoc analysis indicates Ca_V1.2^Tg+; Syn^Tg+ froze less than Ca_V1.2^Tg+; Syn^Tg− and control mice on days 2, 3, and 4. ∗p < .05; Tukey). (A₂) On the day following the context test, mice were placed in a novel context, and freezing was measured during a brief baseline period (pretone) and during the presentation of the same tone previously associated with the foot shock on days 1 to 3 (tone). In contrast to the deficits in memory consolidation for context, mice exhibited freezing levels similar to that observed in littermate control and Ca_V1.2^Tg+; Syn^Tg− mice (effect of training: F_1,60 = 201.2, p < .0001; effect of genotype: F_2,60 = 1.966, p = .1489). To determine to what extent the deficits in context conditioning were due to a failure in acquisition or memory consolidation, a series of additional experiments were performed using 3 separate cohorts of mice (B–D). Mice were placed in the training chambers, and after a brief baseline period, 3 tone-shock pairings were delivered, and after 30 seconds mice were returned to their home cage. Mice were returned to the same context in which they were trained after 1, 6, or 24 hours, and freezing was measured in the absence of tone or shock. (B₁) Compared with baseline, all mice exhibited significant freezing after a 1-hour delay; however, there were no significant differences in freezing levels between the 3 genotypes (effect of training: F_1,33 = 115.8, p < .0001; effect of genotype: F_2,33 = 0.03593, p = .9647). (B₂) All groups exhibited significant freezing during the tone presentation (effect of tone: F_1,33 = 59.12, p < .0001), which did not differ significantly across the 3 genotypes (F_2,33 = 2.729, p = .08). (C₁) Similarly, 6 hours after training, control mice, Ca_V1.2^Tg+; Syn^Tg−, and Ca_V1.2^Tg+; Syn^Tg+ mice all exhibited similar levels of freezing when returned to the training context (effect of training: F_1,46 = 132.4, p < .0001; effect of genotype: F_2,46 = 0.1987, p = .8205). (C₂) When placed into a novel context 24 hours later, all mice exhibited robust freezing during the tone presentation that did not differ across the 3 genotypes (effect of tone: F_1,46 = 52.90, p < .0001; effect of genotype: F_2,46 = 2.311, p = .1105). (D₁) In contrast, when returned to the same context 24 hours after a single contextual fear conditioning session, Ca_V1.2^Tg+; Syn^Tg+ mice exhibited less freezing than their control and Ca_V1.2^Tg+; Syn^Tg− littermates (effect of training: F_1,36 = 199.3, p < .0001; effect of genotype: F_2,36 = 4.323, p = .0208; training × genotype interaction: F_2,36 = 4.331, p = .0206). Post hoc analysis indicates Ca_V1.2^Tg+; Syn^Tg+ mice froze less than Ca_V1.2^Tg+; Syn^Tg− and control mice during the context test 24 hours after training (∗p < .01; Tukey) (D₂) without exhibiting a tone condition deficit (effect of training: F_1,36 = 63.62, p < .0001; effect of genotype: F_2,36 = 2.760, p = .0767). All data are presented as mean ± SEM.