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This has implications not just for understanding basic mechanisms of memory, but also for applications that translate basic research into treatments that may improve clinical options for disorders that involve a debilitating inability to suppress invasive, fearful memories. Evidence for this idea, however, is mixed, with some studies showing no effect or impairments in extinction when it occurs soon after acquisition or retrieval of fear (Morris et al. Many studies have demonstrated that when extinction occurs at least 24 h after initial conditioning (“delayed extinction”), crosstalk between the amygdala and prefrontal cortex mediates lasting changes in performance (Quirk and Mueller 2008; Li et al. In addition, studies of the amygdala and medial prefrontal cortex have begun to show some of the substrates that underlie immediate extinction (Mao et al. ) Mice receiving extinction immediately following acquisition were insensitive to extinction strength (3 or 24 min), whereas mice receiving extinction at a 24-h delay showed more robust response loss in the presence of strong extinction.
Differential activation of m PFC is associated with the immediate extinction deficit.Interestingly, there was no difference between the No Ext group and the delayed extinction groups, indicating that this effect was not generally due to shock prior to c-Fos quantification.In contrast, a main effect of recency ( = 0.02) within the central medial nucleus (Ce M) indicates that while immediate extinction produced greater c-Fos activation, so did being shocked prior to extinction.This extinction process results in the suppression of fear responses, but is generally thought to leave the original fearful memory intact.Here, we investigate the effects of extinction during periods of memory lability on behavioral responses and on expression of the immediate–early gene c-Fos within fear conditioning and extinction circuits. However, little is known about how these specific neuronal populations may be engaged in response to extinction contingencies that result in differential response loss (e.g., immediate or delayed extinction). Second, we examine changes in the product of the immediate early gene, c-Fos, induced by these treatments.These effects were replicated both within and between experiments with consistent results across experiments.
Importantly, control experiments showed that poor extinction produced by immediate extinction was not due to failures to learn extinction contingencies and critically depended on the interval between behavioral manipulations under common testing conditions. Other studies have found opposing results—that extinction soon after acquisition (Myers et al. 2009) promotes the retention of extinction (see Flavell et al. Some of these differences may be attributed to differences in how behavior is assessed (e.g., change in behavior from extinction to test as in Monfils et al.
Mice receiving extinction immediately following acquisition showed decreased freezing relative to a group that received no extinction (No Ext) or extinction outside the conditioning/testing context (Imm-B) when tested 1 d later in the same context they received extinction (Imm-A) (Fig. A main effect of extinction treatment confirmed a difference between groups ( = 0.035, respectively).
This effect was not due to differences in baseline levels of performance as mice undergoing nonreinforced context exposure in Context A and Context B were brought to similar levels of performance by the end of the extinction day ( Immediate extinction does not produce a failure to process the extinction context.
Several recent studies of memory have asked whether extinction under certain conditions can erase, rather than just suppress, previously established memories (Myers et al. Testing following extinction revealed that immediate extinction left behavior more vulnerable to spontaneous recovery even when mice were brought to the same levels of performance following extinction and each test day (Fig. A time × extinction recency interaction confirmed that mice receiving immediate or 24-h extinction were brought to the same levels of performance at the end of extinction and each test ( 0.1 in the final time block of each session).
A significant effect of extinction recency during the first 3 min of the first three tests indicates that mice receiving extinction 24 h following acquisition froze significantly less than those receiving immediate extinction (all = 0.055, respectively).
Mice were brought to similar levels of performance following extinction and test.