Sex- and age-dependent effects of locus coeruleus-originated tau dysfunction on olfaction and neurophysiology in rats
Bibliographic record
Abstract
Abstract Braak and colleagues (2011) described human pretangle stages of abnormal tau protein originating in the locus coeruleus (LC) of young adults (Braak’s Stages a-c, 1a-b), decades prior to the neurofibrillary tangle stages observed in Alzheimer’s disease. To capture the features of LC-originated pretangle tau stages, we used a rat model where male and female TH-Cre +/- rats received bilateral LC infusions of a hyperphosphorylated human tau (htauE14) gene via a viral vector. To assess the effects of age and sex on pretangle stage tau, we assayed physiological and behavioural changes 1-3mo (young) and 12 + mo (aged) post LC-infusion (p.i.). Open field measures revealed age and sex-dependent differences in anxiety in LC-htauE14 infused rats and overall sex- and age-dependent differences in activity. Odour discrimination tests showed little impairment in LC-htauE14 infused rats at 1-3mo after LC infusion. At 12 + mo p.i. however, LC-htauE14 male rats failed a difficult odour discrimination test and a further olfactory detection test (habituation-dishabituation), but male LC-Control rats and female rats were not impaired. LC neuronal firing rates were assessed in urethane-anesthetized aged (12 + mo p.i.) male LC-htauE14 and LC-Control rats. The baseline level of firing of LC neurons in LC-htauE14 rats was higher than firing rates of LC-Control rats. Oscillatory patterns in LC firing were increased in amplitude and frequency by LC-htauE14. PSD95 density measures in piriform cortex were similar for LC-Control and LC-htauE14 male and female rats of young and aged groups. While synaptophysin density was higher in controls of the 1-3mo p.i. groups than in the LC-htauE14 rats, levels did not differ among aged groups. The increased excitability of LC cells observed may occur in relation to reduced LC axon arbours or may reflect a separate effect of htauE14 in LC neurons. The association of increased tonic LC activity to behavioural changes in the pretangle tau rat model merits further investigation.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".