Prediction Error Determines Whether NMDA Receptors in the Basolateral Amygdala Complex Are Involved in Pavlovian Fear Conditioning
Bibliographic record
Abstract
It is widely accepted that activation of NMDA receptors (NMDAR) is necessary for the formation of fear memories in the basolateral amygdala complex (BLA). This acceptance is based on findings that blockade of NMDAR in the BLA disrupts Pavlovian fear conditioning in rodents when initially innocuous stimuli are paired with aversive and unexpected events (surprising foot shock). The present study challenges this acceptance by showing that the involvement of NMDAR in Pavlovian fear conditioning is determined by prediction errors in relation to aversive events. In the initial experiments, male rats received a BLA infusion of the NMDAR antagonist, D-AP5 and were then exposed to pairings of a novel target stimulus and foot shock. This infusion disrupted acquisition of fear to the target when the shock was surprising (experiments 1a, 1b, 2a, 2b, 3a, and 3b) but spared fear to the target when the shock was expected based on the context, time and other stimuli that were present (experiments 1a and 1b). Under the latter circumstances, fear to the target required activation of calcium-permeable AMPAR (CP-AMPA; experiments 4a, 4b, and 4c), which, using electrophysiology, were shown to regulate the activity of interneurons in the BLA (experiment 5). Thus, NMDAR activation is not required for fear conditioning when danger occurs as expected given the context, time and stimuli present, but is required for fear conditioning when danger occurs unexpectedly. These findings are related to current theories of NMDAR function and ways that prediction errors might influence the substrates of fear memory formation in the BLA. SIGNIFICANCE STATEMENTIt is widely accepted that NMDA receptors (NMDAR) in the basolateral amygdala complex (BLA) are activated by pairings of a conditioned stimulus (CS) and an aversive unconditioned (US) stimulus, leading to the synaptic changes that underlie formation of a CS-US association. The present findings are significant in showing that this theory is incomplete. When the aversive US is unexpected, animals encode all features of the situation (context, time and stimuli present) as a new fear/threat memory, which is regulated by NMDAR in the BLA. However, when the US is expected based on the context, time and stimuli present, the new fear memory is assimilated into networks that represent those features, which occurs independently of NMDAR activation in the BLA.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".