Author response: Context-dependent requirement of G protein coupling for Latrophilin-2 in target selection of hippocampal axons
Bibliographic record
Abstract
The complex brain circuits that allow animals to sense and interact with their environment start to form early during development. Throughout this period, neurons extend fiber-like projections to establish precise wiring patterns. Various types of proteins at the surface of both incoming fibers and target cells ensure that only the right partners will connect together. Latrophilin-2, for example, is a neuronal surface protein essential for the formation of accurate connections in the hippocampus, a brain region important for memory. Studded through the membrane of certain neurons, it acts as a signal-sending ligand to direct incoming fibers, with neurons that carry Latrophilin-2 repelling projections from cells that display certain protein partners. At the same time, Latrophilin-2 also allows neurons to receive chemical signals by working with intracellular signaling proteins known as G proteins, which help to relay information between cells. It remained unclear how this role as a signalling receptor participates in the wiring of the hippocampus during development. To explore this question, Pederick, Perry-Hauser et al. examined the impact of Latrophilin-2 on the connection patterns of mouse hippocampal neurons that do not normally carry this protein. Introducing Latrophilin-2 into these ‘proximal CA1 cells’ misdirected them away from their usual partners – unless Latrophilin-2 was altered so that it could not interact with G proteins. In contrast, forcing the connecting partners of CA1 cells to display normal or altered versions of Latrophilin-2 did not interfere with the protein acting as a repulsive ligand. Taken together, these results suggest that the ability of Latrophilin-2 to signal through G proteins is important for neurons that are attempting to project their fibers onto other cells, but not important when Latrophilin-2 acts in targets to direct incoming fibers from other neurons. These results show that a single protein can shape neural circuits by acting both as a signal-receiving receptor and a signal-sending ligand depending on the context. In the future, Pederick, Perry-Hauser et al. hope that their findings will shed new light on how the wiring of the brain is disrupted in neurodevelopmental disorders.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.117 | 0.032 |
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".