Opto-extinction of a threat memory in mice
Bibliographic record
Abstract
Memories of past experiences guide future behaviour. Sparse ensembles of neurons, known as engrams, are thought to store memories in the brain. Neurons involved in a particular engram ("engram neurons") are necessary for subsequent memory expression as memory retrieval is thought to be initiated by an external sensory cue reactivating engram neurons. However, conditions or environments are dynamic, such that future behaviour should be flexible. The role of engrams in mediating flexible behaviour is not understood. Here we examined this question using one type of flexible behaviour, extinction of a threat response. An initially neutral tone is first paired with an aversive footshock such that the tone alone induces defensive freezing. After subsequent repeated tone presentations without the footshock, rodents no longer freeze to the tone. Because the tone cue is thought to reactivate the engram to induce memory retrieval, we examined whether it is possible to induce an extinction-like behavioural effect by optogenetically reactivating the lateral amygdala component of the engram alone (without tone re-exposure). Similar to tone-induced extinction, mice showed decreased freezing to optogenetic stimulation of the lateral amygdala engram in the "extinction training" session. Moreover, "opto-extinguished" mice showed decreased freezing to the tone when subsequently tested for retrieval of the extinction training in the same context, suggesting that the opto-extinction transferred to the actual sensory stimulus. However, unlike tone extinction, in which mice showed renewal of tone-induced freezing when tested in a novel context, opto-extinguished mice continued to show a deficit in tone-induced freezing. Extinction has been characterized as new learning that inhibits the original memory or a phenomenon in which the original memory is "unlearned". Our findings suggest that opto-extinction may silence the original engram to "unlearn" the original memory.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".