Prediction Error Determines Whether NMDA Receptors in the Basolateral Amygdala Complex Are Involved in Pavlovian Fear Conditioning

Williams-Spooner, Matthew J.; Delaney, Andrew; Westbrook, R. Frederick; Holmes, Nathan M.

doi:10.1523/jneurosci.2156-21.2022

Cited by 11 publications

(6 citation statements)

References 40 publications

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“…Consistent with previous findings (Leidl et al, 2018, Williams-Spooner et al, 2019, Williams-Spooner et al, 2022), both groups froze at similar levels when tested with the S2 or the S1 (Figure 2D-E). Statistical analyses confirmed there was no effect of drug on freezing levels to either the S2 ( F (1, 23) = 0.42, Fc = 4.28, p = 0.53) or the S1 ( F (1, 23) = 0.29, Fc = 4.28, p = 0.60), indicating that the intra-BLA CHX infusion did not disrupt consolidation of fear to either stimulus.…”

Section: Resultssupporting

confidence: 92%

“…Finally, is important to recognize parallels between the present findings and those reported in previous studies examining the involvement of NMDA receptors in the encoding of a second dangerous experience (Crestani et al, 2018;Williams-Spooner et al, 2022). These studies show that encoding of a second dangerous experience does not require NMDA receptors in the BLA or hippocampus when it occurs within 2-3 days of a similar dangerous experience, but does require .…”

Section: Discussionsupporting

confidence: 82%

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Contextual and temporal regulation of fear memory consolidation in the basolateral amygdala complex

Leake

Cardona

Westbrook

et al. 2022

Preprint

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It is widely accepted that fear memories are consolidated through protein synthesis-dependent changes in the basolateral amygdala complex (BLA). However, recent studies show that protein synthesis is not required to consolidate the memory of a new dangerous experience when it is similar to a prior experience. Here, we examined whether the protein synthesis requirement for consolidation of the new experience varies with its spatial and temporal distance from the prior experience. In each experiment, rats were conditioned to fear a stimulus (S1, e.g., light) across its pairings with shock in stage 1; and a second stimulus (S2, e.g., tone) that preceded additional S1-shock pairings (S2-S1- shock) in stage 2. The latter stage was followed by a BLA infusion of a protein synthesis inhibitor, cycloheximide or vehicle. Finally, rats were tested for fear to S2. Critically, protein synthesis in the BLA was not required to consolidate fear to S2 when the two training stages occurred 48 hours apart and in the same context; was required when the two training stages were separated by a 14-day delay or occurred in different contexts; but was again not required when rats were re-exposed to S1 or shock after the delay or in the different context. Thus, protein synthesis in the BLA is not always required to consolidate a new fear memory. Instead, this requirement is determined by the degree of similarity between present and past experiences, the time and place in which those experiences occur, as well as reminders of the past experience.

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Section: Resultssupporting

confidence: 92%

Section: Discussionsupporting

confidence: 82%

Contextual and temporal regulation of fear memory consolidation in the basolateral amygdala complex

Leake

Cardona

Westbrook

et al. 2022

Preprint

Self Cite

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“…whereas the fear memory produced by pairings of an auditory or visual stimulus with foot shock (e.g., light-shock) requires activation of NMDA receptors in the BLA (Bauer et al, 2002;Keidar et al, 2023;Rodrigues et al, 2001;Williams-Spooner et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

Integration of sensory and fear memories in the rat medial temporal lobe: advancing research by Wong et al. (2019)

Wong,

Thomas,

Killcross

et al. 2024

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Wong et al. (2019) used a sensory preconditioning protocol to examine how sensory and fear memories are integrated in the rat medial temporal lobe. In this protocol, rats integrate a sound-light (sensory) memory that forms in stage 1 with a light-shock (fear) memory that forms in stage 2 to generate fear responses (freezing) across test presentations of the sound in stage 3. Here, we advance this research by showing that: 1) how/when rats integrate the sound-light and light-shock memories (online in stage 2 or at test in stage 3) changes with the number of sound-light pairings in stage 1; and 2) regardless of how/when it occurs, the integration requires communication between two regions of the medial temporal lobe: the perirhinal cortex and basolateral amygdala complex. Thus, “event familiarity” determines how/when sensory and fear memories are integrated but not the circuitry by which the integration occurs: this remains the same.

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“…Also, dopamine neurons innervate the BLA and promote second-order fear conditioning via the dopamine D1 receptor 24 . Infusion of a NMDAR antagonist in BLA is critical for acquisition of second-order memory when the expected shock is omitted 63 . CGRP PBN neurons may play a similar role in aversive learning as dopamine neurons play in appetitive learning.…”

Section: Discussionmentioning

confidence: 99%

ParabrachialCalcaneurons mediate second-order conditioning

Park,

Zhu,

Cao

et al. 2024

Preprint

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Learning to associate cues, both directly and indirectly, with biologically significant events is essential for survival. Second-order conditioning (SOC) involves forming an association between a previously reinforced conditioned stimulus (CS1) and a new conditioned stimulus (CS2) without the presence of an unconditioned stimulus (US). The neural substrates mediating SOC, however, remain unclear. In the parabrachial nucleus,Calcagene-expressing neurons, which react to the noxious US, also respond to a CS after its pairing with a US. This observation led us to hypothesize their involvement in SOC. To explore this possibility, we established an aversive SOC behavioral paradigm in mice and monitoredCalcaneuron activity via single-cell calcium imaging during SOC and subsequent recall phases. These neurons were activated not only by CS1 following its association with the US but also by CS2 after SOC. Chemogenetically inhibiting these neurons during second-order associations attenuated SOC. These findings suggest that activating the US pathway in response to a learned CS plays an important role in forming the association between the old and a new CS, promoting the formation of second-order memories.

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Prediction Error Determines Whether NMDA Receptors in the Basolateral Amygdala Complex Are Involved in Pavlovian Fear Conditioning

Cited by 11 publications

References 40 publications

Contextual and temporal regulation of fear memory consolidation in the basolateral amygdala complex

Contextual and temporal regulation of fear memory consolidation in the basolateral amygdala complex

Integration of sensory and fear memories in the rat medial temporal lobe: advancing research by Wong et al. (2019)

ParabrachialCalcaneurons mediate second-order conditioning

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