The leptin receptor, a driver of adult neurogenesis that may treat Alzheimer's disease, has been found in murine dentate granule Cells' ciliary toolbox
Bibliographic record
Abstract
This is a story about the dentate gyrus's (gyrus dentatus) granule cells that are parts of the hippocampal memories-recording machinery in the brain's temporal lobes. These little cells, each with its single immobile cilium, share, with hippocampal CA3 pyramidal neurons, data from entorhinal cortical neurons that receive streams of data from the brain's many sensory regions about external happenings. There are many on-going efforts to understand how the granule cells separate potentially overlapping, hence potentially interfering, trains of similar data into separate threads or circuits with which CA3 and CA1 neurons can produce unique activity patterns and thus distinct instead of distorted memories. These patterns are then sent up in polymodal chunks to sites in the neocortex from which they can later be reassembled when needed into the original or with elapsed time and frequent accessing increasingly modified memories. These granule cells are very different from other neurons: in fact, they are born as tabulae rasae neurons open for novel input in adult rodent, human and other mammalian brains. They then grow old and synaptically loaded with memories. However, while the modellers have focussed on the contributions of the successive batches of adult-born dentate gyral granule cells to memory formation, they have ignored what appears to be another of these cells' special characteristics, i.e., loading potent adult neurogenesis-driving tools such as the SSTR3 receptor and the pan-neurotrophin p75NTR receptor into their cilia. Now we have found that they also put the functional leptin receptor, LepRb (ObRb), into their ciliary toolboxes. We looked for the leptin receptor in the cilium's toolbox for two reasons: the already established involvement of cilia in adult neurogenesis and the reported ability of leptin to stimulate adult neurogenesis in the dentate gyri of normal and transgenic Alzheimer's disease model mice. Thus, further study may show that signals from the granule cell's LepRb may be able to slow or even stop the hippocampal damage and cognitive impairment of Alzheimer's disease, an intracerebrally spreading neuronal connectome-opathy. However, at least until then, it seems obvious that we will never be able to understand the dentate gyrus's critical roles in adult neurogenesis and memory formation without knowing how its granule cells use the battery of tools in their single cilia.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".