Bibliographic record
Abstract
Experience with drugs of abuse (such as cocaine) produces powerful, long-lasting memories that may be key in the development and persistence of drug addiction. The neural mechanisms that mediate how and where these cocaine-cue memories are encoded, consolidated, and stored in the brain are unknown. Here we used cocaine-induced conditioned place preference to examine the precise neural circuits that support a cocaine-cue memory (cocaine-cue “memory trace” or “engram”) in mice. We found that a small population of neurons (~10%) in the lateral nucleus of the amygdala (LA) was recruited at the time of cocaine-conditioning to become part of the cocaine-cue engram supporting that memory. Moreover, neurons with increased levels of the transcription factor CREB (cAMP response element-binding protein) were preferentially recruited or allocated to the cocaine-cue engram. Pre-test ablation or silencing of neurons overexpressing CREB (but not a similar number of LA neurons not allocated to the cocaine-cue memory engram) disrupted the expression of a previously acquired cocaine-cue memory, suggesting that neurons overexpressing CREB become critical nodes in the LA of what is likely a larger (perhaps brain-wide) cocaine-cue engram. Previous research has suggested that coordinated post-encoding reactivation of neurons within an engram or cell assembly is crucial for memory consolidation (Marr, 1971; Buzsáki, 1989; Wilson McNaughton, 1994; McClelland et al., 1995; Girardeau et al., 2009; Dupret et al., 2010; Carr et al., 2011). Consistent with this, we also found that post-training suppression or non-discriminate activation of CREB overexpressing neurons impaired consolidation of the cocaine-cue memory. We also showed that these neurons were important for the reinstatement of a cocaine-cue memory. Following extinction of a cocaine-cue memory, re-exposure to cocaine may reinstate the original memory (Brown et al., 2010; Bilbao et al., 2008; Mueller Stewart, 2000). These results suggest that those neurons that are initially important in a cocaine-cue memory continue to be important to that memory, even following extinction. Finally, we found that in the LA, neurons that have relatively higher levels of neuronal excitability are more likely to be recruited to an engram supporting a cocaine-cue memory. Together, these findings reveal mechanisms underlying how and where drug memories are encoded and stored in the brain.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.004 | 0.001 |
| Science and technology studies | 0.002 | 0.003 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.005 | 0.002 |
| Research integrity | 0.007 | 0.009 |
| Insufficient payload (model declined to judge) | 0.022 | 0.009 |
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".