Previous studies showed that, similar to human declarative memory, contextual fear memory in rodents undergoes a consolidation process. Recent fear memory (i.e., memory in the

days following the memorable event) depends on hippocampal function, whereas remote memory (i.e., memory after several weeks) operates independently of hippocampal function (Frankland and Bontempi, 2005, Frankland et al., 2004, Kim and Fanselow, 1992 and Squire et al., 2004). Therefore, we carried out our experiments using two protocols. First, to monitor learn more recent memories, we injected AAVs into the hippocampus 30 days before training and tested memory 1–2 days after training (Figure 4A). Second, to monitor remote memories, we injected AAVs into the hippocampus 7–10 days after training and tested memory 27–30 days after the injection (i.e., ∼36 days after training; Figure 4E). In tests of recent memory (Figures 4B–4D), hippocampal TetTox severely impaired contextual memory, consistent with previous studies demonstrating that the hippocampus is critical for contextual fear learning (Fanselow and Dong, 2010, Kim and Fanselow,

1992 and Wiltgen et al., 2006). However, the Syt1 KD caused no significant impairment Selleck Sunitinib in contextual memory (Figure 4B). In the altered-context test,

the hippocampal Syt1 KD produced an increased fear response, suggesting that the Syt1 KD impaired the mouse’s ability to recognize the context as different (Figure 4C), consistent with its electrophysiologically demonstrated effectiveness (Figure 3). Because TetTox blocks contextual fear conditioning (Figure 4B), it does not result in an increased fear response in the altered context (Figure 4C). Furthermore, as expected, neither the Syt1 KD nor TetTox produced a significant change in cued fear conditioning (Figure 4D). No alterations of spontaneous behaviors were observed in the injected mice, as assessed by quantitative actometer not measurements (Figure S3; Fowler et al., 2001 and Fowler et al., 2003). The fact that contextual fear memory is normal after the hippocampal Syt1 KD but is blocked by TetTox strongly suggests that CA1 neurons can rely on bulk synaptic transmission induced by bursts of spikes for transmitting information to their downstream targets during fear conditioning learning. Consistent with previous work suggesting that the hippocampus does not play a major role in remote memories (Fanselow and Dong, 2010, Frankland and Bontempi, 2005, Frankland et al.