Protein synthesis in the basolateral amygdala complex is required for consolidation of a first-order fear memory, but not for consolidation of a higher-order fear memory

Leidl, Dana M.; Lay, Belinda P. P.; Chakouch, Cassandra; Westbrook, R. Frederick; Holmes, Nathan M.

doi:10.1016/j.nlm.2018.04.001

Cited by 17 publications

(26 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This experiment sought to replicate and extend the finding reported by Leidl et al (2018) that the presence of an already-fearconditioned S1 in the S2-S1-shock protocol alters the protein synthesis requirement for consolidation of fear to S2. Four groups of rats were exposed to S1-shock pairings in Stage 1, S2-S1-shock sequences (serial-order conditioning) in Stage 2, and were then tested for fear to S2 and S1 in Stage 3.…”

Section: Experiments 2amentioning

confidence: 81%

“…Rats received four presentations of the sequence S2-S1-shock (serial-order conditioning) on day 3. The durations of S2 and S1 were those used in previous studies of second-order and serial-order (Leidl et al, 2018) conditioning. Offset of the 30 s S2 co-occurred with onset of the 10 s S1, which coterminated in foot shock.…”

Section: Methodsmentioning

confidence: 99%

“…The differential protein synthesis requirement for consolidating first-and second-order fears is not due to the presence of shock in first-order conditioning and its absence in second-order conditioning (Leidl et al, 2018). This was confirmed using a conditioning protocol in which rats were exposed to S1-shock pairings in Stage 1, and then to the sequence S2-S1-shock (serialorder conditioning) in Stage 2: that is, S2 was paired with S1 as in second-order conditioning, but S1 continued to be paired with shock as in first-order conditioning.…”

Section: Introductionmentioning

confidence: 97%

“…In each case, rats express what is learned about S1 and S2 in autonomic and defensive responses indicative of fear in people (Davis, 1992;Fanselow, 1998;McNally and Westbrook, 2006). Following Pavlov (1927), the fear elicited by S1 is termed first-order conditioned fear, and that elicited by S2 is termed second-order conditioned fear (Rizley and Rescorla, 1972;Yin et al, 1994;Parkes and Westbrook, 2010;Witnauer and Miller, 2011;Holmes et al, 2013Holmes et al, , 2014Leidl et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Conditions under Which Consolidation of Serial-Order Conditioned Fear Requires De Novo Protein Synthesis in the Basolateral Amygdala Complex

2019

Self Cite

View full text Add to dashboard Cite

Consolidation of conditioned fear to a stimulus (S1) paired with shock requires de novo protein synthesis in the basolateral amygdala complex (BLA), whereas consolidation of conditioned fear to a stimulus (S2) paired with the fear-eliciting S1 requires DNA methylation but not de novo protein synthesis in the BLA. The present experiments merged these protocols by exposing rats to pairings of a serial S2-S1 compound and shock to examine if/when protein synthesis in the BLA is required to consolidate fear to S2. Rats received a BLA infusion of the protein synthesis inhibitor, cycloheximide, immediately after the S2-S1-shock session and were subsequently tested with S2. The infusion disrupted consolidation of fear to S2 when there had been no prior training of S1 (Experiment 1), the prior training had consisted of unpaired presentations of S1 and shock (Experiment 4), or in pairings of S1 and sucrose (Experiment 5). Consolidation of fear to S2 was unaffected by the infusion of cycloheximide but was disrupted by the DNA methyltransferase inhibitor, 5-AZA, when S1 had been previously fear-conditioned (Experiments 2a, 2b, and 3). These findings imply that what has already been learned about S1 determines the BLA processes that consolidate fear to S2. The already-fear-conditioned S1 blocks the S2-shock association that otherwise forms (and whose consolidation requires de novo protein synthesis in the BLA) while simultaneously acting as a learned source of danger for its S2 associate (whose consolidation requires DNA methylation but not de novo protein synthesis in the BLA).

show abstract

Section: Experiments 2amentioning

confidence: 81%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Conditions under Which Consolidation of Serial-Order Conditioned Fear Requires De Novo Protein Synthesis in the Basolateral Amygdala Complex

2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…First, unlike in sensory preconditioning where the two component memories are encoded and stored in distinct regions of the MTL (Holmes et al, 2013), both of the component memories in second-order conditioning are encoded and stored in the BLA (Holmes et al, 2013; Parkes and Westbrook, 2010). Second, unlike in sensory preconditioning, where consolidation of the integrated (or mediated) sound-shock memory requires de novo protein synthesis in the PRh, consolidation of the integrated second-order memory occurs independently of de novo protein synthesis in the BLA (Lay et al, 2018; Leidl et al, 2018). These differences show that the order in which information is presented (or processed) determines how distinct memories are encoded and stored in the MTL, as well as the mechanisms involved in their integration.…”

Section: Discussionmentioning

confidence: 99%

'Online' integration of sensory and fear memories in the rat medial temporal lobe

Wong

Westbrook

Holmes

2019

eLife

View full text Add to dashboard Cite

How does a stimulus never associated with danger become frightening? The present study addressed this question using a sensory preconditioning task with rats. In this task, rats integrate a sound-light memory formed in stage 1 with a light-danger memory formed in stage 2, as they show fear when tested with the sound in stage 3. Here we show that this integration occurs ‘online’ during stage 2: when activity in the region that consolidated the sound-light memory (perirhinal cortex) was inhibited during formation of the light-danger memory, rats no longer showed fear when tested with the sound but continued to fear the light. Thus, fear that accrues to a stimulus paired with danger simultaneously spreads to its past associates, thereby roping those associates into a fear memory network.

show abstract

The role of the basolateral amygdala and infralimbic cortex in (re)learning extinction

et al. 2018

View full text Add to dashboard Cite

The basolateral amygdala complex (BLA) and infralimbic region of the prefrontal cortex (IL) play distinct roles in the extinction of Pavlovian conditioned fear in laboratory rodents. In the past decade, research in our laboratory has examined the roles of these brain regions in the re-extinction of conditioned fear: i.e., extinction of fear that is restored through re-conditioning of the conditioned stimulus (CS) or changes in the physical and temporal context of extinction training (i.e., extinction of renewed or spontaneously recovered fear). This paper reviews this research. It has revealed two major findings. First, in contrast to the acquisition of fear extinction, which usually requires neuronal activity in the BLA but not IL, the acquisition of fear re-extinction requires neuronal activity in the IL but can occur independently of neuronal activity in the BLA. Second, the role of the IL in fear extinction is determined by the training history of the CS: i.e., if the CS was novel prior to its fear conditioning (i.e., it had not been trained), the acquisition of fear extinction does not require the IL; if, however, the prior training of the CS included a series of CS-alone exposures (e.g., if the CS had been pre-exposed), the acquisition of fear extinction was facilitated by pharmacological stimulation of the IL. Together, these results were taken to imply that a memory of CS-alone exposures is stored in the IL, survives fear conditioning of the CS, and can be retrieved and strengthened during extinction or re-extinction of that CS (regardless of whether the extinction is first- or second-learned). Hence, under these circumstances, the initial extinction of fear to the CS can be facilitated by pharmacological stimulation of the IL, and re-extinction of fear to the CS can occur in the absence of a functioning BLA.

show abstract

Protein synthesis in the basolateral amygdala complex is required for consolidation of a first-order fear memory, but not for consolidation of a higher-order fear memory

Cited by 17 publications

References 49 publications

The Conditions under Which Consolidation of Serial-Order Conditioned Fear Requires De Novo Protein Synthesis in the Basolateral Amygdala Complex

The Conditions under Which Consolidation of Serial-Order Conditioned Fear Requires De Novo Protein Synthesis in the Basolateral Amygdala Complex

'Online' integration of sensory and fear memories in the rat medial temporal lobe

The role of the basolateral amygdala and infralimbic cortex in (re)learning extinction

Contact Info

Product

Resources

About