Early Odor Preference Learning in the Rat: Bidirectional Effects of cAMP Response Element-Binding Protein (CREB) and Mutant CREB Support a Causal Role for Phosphorylated CREB
Bibliographic record
Abstract
Early odor preference learning in rats is associated with increases of phosphorylated CREB (pCREB) in mitral cells of the olfactory bulb. In the present study, herpes simplex virus expressing CREB (HSV-CREB) and dominant-negative mutant CREB (HSV-mCREB) have been injected into the bulb to assess a causal role for CREB and pCREB in this model. Odor paired with stroking or with the beta-adrenoceptor agonist isoproterenol produces odor approach 24 hr later. Isoproterenol-induced learning exhibits an inverted U curve dose-dependent learning relationship with both low and high doses failing to produce learning. pCREB increases have only been seen at the learning effective dose. In the present study, injection of an HSV vector expressing mutant CREB into the olfactory bulb prevented learning induced by stroking. Control HSV expressing LacZ was without effect. Expression of mutant CREB shifted the dose-learning curve for isoproterenol to the right such that a higher dose was required to induce learning. Expression of CREB shifted the dose-learning curve for isoproterenol to the left, with a lower dose now producing learning. As expected from this shift, CREB overexpression interfered with learning induced by stroking. When learning occurred, with either CREB or mutant CREB, pCREB was observed to be elevated relative to the nonlearning LacZ control groups. Unexpectedly, with odor plus stroking in the nonlearning CREB group, the level of pCREB was also higher than with odor plus stroking in LacZ controls that did learn. The data demonstrate a causal role for CREB and pCREB in early mammalian odor preference learning, reinforcing CREB as a "universal" memory molecule. They support evidence that CREB overexpression can be deleterious and suggest the hypothesis of an optimal pCREB window for learning.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.009 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".