Loss of the neuronal kinase DCLK3 leads to anxiety-like behaviour and memory deficits
Bibliographic record
Abstract
DCLK3 (Doublecortin-like kinase 3) is a kinase preferentially expressed in neurons. Dclk3 variants are risk factors for psychiatric disorders and brain alterations linked to age-related mild cognitive impairment, suggesting that this kinase could be important to cognition. However, the physiological role of DCLK3 remains unknown. Here, we generated and characterized mice with constitutive or brain region-specific Dclk3 knockout. We found that constitutive pan-deletion of Dclk3 is associated with an anxiety phenotype in males, associated with changes in brain metabolites in the absence of major neuroanatomical alterations, motor deficits or memory deficits. Moreover, virally mediated loco-regional conditional Dclk3 knockout in the dorsal hippocampus of adult mice led to spatial memory deficits and transcriptomic changes, characterized by increased expression of α2, β1 and β2 subunits of the GABAA receptor, downregulation of neuronal activity-regulated genes, such as the immediate early genes (e.g. Egr1, Fos, Per1 and Nr4r1), and transcriptional regulator activity enriched in polycomb-repressive complexes. These new data reveal that Dclk3 modulates behaviour and cognition in association with transcriptomic changes in the hippocampus, providing direct physiological evidence that this kinase is involved in synaptic plasticity, consistent with its crucial role in neurodegenerative and psychiatric diseases.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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".