Characterization of Fear Memory Reconsolidation

“Most of these studies use protein synthesis inhibitors, or other pharmacological agents, that are not safe for use in humans 3,4,6,11–14 .”

“Following reactivation and blockade of reconsolidation, previously learned behaviors are still intact 2 hours (Suzuki et al. 2004) and 4 hours (Debiec et al. 2002, Duvarci & Nader 2004, Nader et al. 2000) later, with no sign that degradation has begun.”

“However, amnesic animals can be retrained, demonstrating that the targeted brain structures remain functiona”

“Many recent studies have found that the deficits of memory after post-retrieval manipulations can last for at least 14 days (30 days in some studies), and studies utilizing localized infusions often report long-lasting memory decrement”

“[320]; Duvarci and Nader [321]), of the representation of the original experience by the hippocampus could produce a hypermnesic (strengthening) of the memory of”

“Second, many studies have explicitly tested for, and failed to show, spontaneous recovery, reinstatement, and state-dependent learning [97].”

“using reinforced reactivation procedures in fear conditioning [48, 57], and in many [35, 58], but not all [59] studies of object recognition memories).”

“Following reactivation and blockade of reconsolidation, previously learned behaviors are still intact 2–4 h later [26,27,31,32].”

“Importantly, these studies show that the blockade of reconsolidation is specific to the fear memory reactivated, leaving other memories intact (Doyere et al, 2007), and that fear memories do not return with passage of time, the alteration of contextual cues, or additional stress (Duvarci and Nader, 2004).”

“Finally, we discuss how research on genetic animal models of impaired extinction can further our understanding of the molecular and genetic bases of human anxiety disorders.”

“Tukey’s test was selected for post hoc analyses, and a significance level of p 0.05 was selected for all analyses.”

“com which is unexpected of extinction [5].”

“The second protocol used was a reinforced trial that has been shown to induce reconsolidation in the LB”

“…from original learning, which is almost inevitable in exposure therapy, reconsolidation may not be induced but rather a new memory trace is formed (Besnard, 2012; Bozon et al., 2003; Debiec et al., 2006; Hupbach et al., 2009; Osan et al., 2011; but see Duvarci and Nader, 2004; Nader et al., 2000).”

“Reconsolidation of fear memory has been shown to be mediated by the amygdala (Nader et al., 2000; Duvarci and Nader, 2004; Tronel et al., 2005; Lee et al., 2006) and hippocampus (Debiec et al.”

“, reactivation), accompanied by a so-called amnestic agent, results in its apparently permanent weakening, as evidenced by its not undergoing renewal, reinstatement, or spontaneous recovery (8), suggesting that the memory has been eliminated.”

“It has been recently proposed that in order to demonstrate that a behavioral impairment is attributable to consolidation blockade, and not nonspecific effects of a manipulation , intact short-term memory must be demonstrated (Dudai 2004; also see, Duvarci and Nader 2004).”

“Studies have demonstrated that post-reactivation infusions of anisomycin into the BLA disrupt retention of auditory fear memories when animals are tested 24 h later (Duvarci and Nader, 2004; Duvarci et al, 2006; Nader et al, 2000; Parsons et al, 2006).”

“As such, extinction can be differentiated from forgetting or failures to reconsolidate, which involve erasure (Duvarci and Nader, 2004).”

“2004) suggest that reconsolidation is engaged when unexpected events occur, it is pertinent to note that demonstrations of reconsolidation have also been shown using the identical stimuli as was employed during training (Duvarci and Nader 2004; Eisenberg and Dudai 2004).”

“fore, if low level of freezing during Ext Rec was due to impaired reconsolidation then we would expect to see impaired fear renewal in Paired-ChR2 group (Duvarci and Nader, 2004).”

“…have provided a detailed neural and behavioral characterization of post-retrieval memory modification, describing a large cast of molecular mechanisms ( Tronson and Taylor, 2007 ) and several boundary conditions on its occurrence ( Dudai, 2012 ; Duvarci and Nader, 2004 ; Nader and Hardt, 2009 ).”

“Accumulated experimental data support the argument that after retrieval, consolidated memory may become temporarily vulnerable to disruption for a limited period of time (Przybyslawski and Sara, 1997; Przybyslawski et al, 1999; Nader, 2003; Debiec and Ledoux, 2004; Duvarci and Nader, 2004).”

“In contrast to the findings of Duvarci and Nader [11], in our study the freezing level reached its maximum after a single training trial, indicating that the CS-US association was fully learned; the additional CS-US trial during reactivation with no change in the temporal structure was therefore not sufficient to trig…”

“Importantly, in a related study reconsolidation was found to occur even if the reinforcer was not withdrawn during retrieval, a condition in which reactivation represents a conditioning rather than an extinction trial (Duvarci and Nader, 2004).”

“Extinction of a fear memory can be reversed by exposure to a ‘‘reminder shock” that is below the threshold for de novo fear conditioning, whereas reconsolidation effects cannot (Cai et al., 2006; Duvarci & Nader, 2004).”

“…obtained (Sara 2000; Berman and Dudai 2001; Vianna et al. 2001; Anokhin et al. 2002; Kida et al. 2002; Milekic and Alberini 2002; Bahar et al. 2003, 2004; Koh and Bernstein 2003; Biedenkapp and Rudy 2004; Cammarota et al. 2004b; Duvarci and Nader 2004; Fischer et al. 2004; Lattal and Abel 2004).”

“However, in other models the labilization-reconsolidation process seems to be triggered in the presence of the reinforcement (Duvarci & Nader, 2004).”

“By 6 h the reconsolidation process is complete (Nader et al., 2000; Duvarci and Nader, 2004).”

“These are called “re-consolidation”, when the conditions favour the permanence of the trace (Debiec et al. 2002; Duvarci and Nader 2004; Sara 2000), and “extinction”, when the conditions indicate that the memory has no reason to persist any longer (Myers and Davis 2002; Quirk and Mueller 2008).”

“fear reinstatement session in a novel context (Chamber C), consisting of exposure to three unsignaled footshocks (Duvarci and Nader 2004), followed 24 h later by a third test of PR-LTM in Chamber B (Reinstatement Test).”

“During reconsolidation that require protein synthesis, the original memory is thought to update or integrate new information into long-term memories (Alberini, 2005; Debiec, LeDoux, & Nader, 2002; Dudai, 2004; Duvarci & Nader, 2004; Nader, 2003; Nader, Schafe, & Le Doux, 2000; Sara, 2000).”

“There is a vast literature in rats reporting erasing of fear by targeting the amygdala with protein synthesis inhibitors after memory retrieval [24].”

“1982a) or to a second training trial (Sangha et al. 2003; Duvarci and Nader 2004; Eisenberg and Dudai 2004).”

“Recently under conditions in which competition between memories does not take place, Duvarci and Nader (2004) and Bozon et al. (2003) found impairment over a previously consolidated memory, by using a retrieval session identical to the training session.”

“Extinction training usually consisted of CS-alone trials that induced memory retrieval and reconsolidation (Nader et al., 2000; Duvarci and Nader, 2004).”

“process (Sara 2000;Duvarci and Nader 2004).”

“…following the blockade of memory reconsolidation has traditionally been the criteria for determining if the reduction in memory performance is due to reconsolidation or extinction processes (Duvarci, Mamou, and Nader, 2006; Duvarci and Nader, 2004; Power, Berlau, McGaugh, and Steward, 2006).”

“Thus, in theory, memory would not return after a block of reconsolidation (Duvarci and Nader 2004).”

“However, other studies have not confirmed these results (Bozon et al., 2003; Duvarci & Nader, 2004).”

“Recent studies have shown that fear memories, when reactivated or retrieved, return to a labile state in the LA and require protein synthesis for reconsolidation (Nader et al., 2000; Duvarci and Nader, 2004).”

“reexposure to this context could engage either extinction or reconsolidation processes (Duvarci and Nader 2004), we also investigated the effects of inhibiting glutamate- and NO-mediated”

“2006), whereas others have found no evidence of recovery (Duvarci and Nader, 2004; Lee et al., 2004).”

“In one notable example, Duvarci and Nader (2004) injected anisomycin into the BLA following the reactivation of an auditory-cue fear memory.”

“Taken together, the studies with animal models reveal that such incongruence may be given by qualitative and quantitative differences [19,34,37].”

“, 2004), and the labile or instable period of the reconsolidation persists for several hours post-memory retrieval (Duvarci and Nader, 2004).”

“and protein synthesis inhibitors have been used to successfully impede the storage of retrieved auditory fear memories in rodents.(129) However, because of the high toxicity rates of protein synthesis inhibitors as potential drugs, pharmacological interventions targeted at the reconsolidation processes have been large…”

“…specific to the fear memory reactivated, leaving other memories intact (Doyere et al., 2007), and that the disruption of the fear memories was enduring in nature, not returning following the alteration of contextual cues, after the passage of time, or additional stress (Duvarci and Nader, 2004).”

“Other studies, however, have demonstrated disruption of reconsolidation when a training trial is used as reactivation [65].”

“Furthermore, reconsolidation-like effects have been reported when the reminder involves reinforced trials (and thus no prediction error) in both nonhuman animals (47) and humans (12), and impairment effects are absent even in studies where prediction error would be expected (44, 45).”

“…for at least 22 days, it agrees with convergent evidence indicating that interventions affecting reconsolidation induce a longlasting outcome (Duvarci and Nader, 2004; Stern et al., 2012), and supports the premise that THC could represent an interesting therapeutic approach to attenuate not…”

“These innervations of the basolateral amygdala may be related to learning and memory (Abe et al., 2009; Duvarci and Nader, 2004; Ehrlich et al., 2009; Maren, 2008).”

“Thus, several reports indicate that anisomycin permanently disrupts reactivated memories ( Duvarci and Nader 2004 ).”

“In some studies, a reinforced memory reactivation session has been used to rule out facilitation of extinction learning (Duvarci & Nader, 2004).”

“…motivated learning requires protein synthesis or the function of specific molecules in the amygdala (Nader et al. 2000b; Koh and Bernstein 2003; Duvarci and Nader 2004; Wang et al. 2005; Bucherelli et al. 2006; Lee et al. 2006a,b; Lin et al. 2006; Tronson et al. 2006; but see Bahar et al.…”

“The contradiction between the SPH and the continuous incorporation of new neurons into the hippocampal circuits was highlighted by Nottebohm (2002) as follows: ‘‘A theory of learning based on synapses did not predict a need for replacing healthy adult neurons by other neurons of the same kind, and…”

“…there have been theoretical accounts proposed for the differences in the effects of protein synthesis during extinction (Dudai and Eisenberg 2004; Duvarci and Nader 2004; Fischer et al 2004; Power et al 2006), the mechanisms that cause rapid behavioral extinction when protein synthesis is…”

“Reminder treatments also produce recovery from amnesia that had been induced by amnestic agents administered following reactivation of an old memory (see Eisenberg and Dudai 2004 as well as Duvarci and Nader 2004).”

“Extinction is thought to reflect the formation of new inhibitory memories (Myers and Davis, 2002; Duvarci and Nader, 2004; Quirk and Mueller, 2008).”

“Previous studies suggest that the basolateral nucleus of the amygdala (BLA) is mainly involved in reconsolidation (Nader et al, 2000; Duvarci and Nader, 2004; Baldi et al, 2008), and that the amygdala, hippocampus, and medial prefrontal cortex (mPFC) form a circuit necessary for extinction in rodents (for review, see…”

“Auditory-cued fear conditioning (FC) was carried out as previously described (18,33) with some modifications as described in the supplement 2 material.”

“Indeed, neuroscience has shown that re-accessing memories generally changes them, rather than enforces them (Duvarci and Nader, 2004).”