Relaxin‐3 inputs target hippocampal interneurons and deletion of hilar relaxin‐3 receptors in “floxed‐RXFP3” mice impairs spatial memory
Bibliographic record
Abstract
ABSTRACT Hippocampus is innervated by γ‐aminobutyric acid (GABA) “projection” neurons of thenucleus incertus(NI), including a population expressing the neuropeptide, relaxin‐3 (RLN3). In studies aimed at gaining an understanding of the role of RLN3 signaling in hippocampus via its Gi/o‐protein‐coupled receptor, RXFP3, we examined the distribution of RLN3‐immunoreactive nerve fibres and RXFP3 mRNA‐positive neurons in relation to hippocampal GABA neuron populations. RLN3‐positive elements were detected in close‐apposition with a substantial population of somatostatin (SST)‐ and GABA‐immunoreactive neurons, and a smaller population of parvalbumin‐ and calretinin‐immunoreactive neurons in different hippocampal areas, consistent with the relative distribution patterns of RXFP3 mRNA and these marker transcripts. In light of the functional importance of the dentate gyrus (DG) hilus in learning and memory, and our anatomical data, we examined the possible influence of RLN3/RXFP3 signaling in this region on spatial memory. Using viral‐based Cre/LoxPrecombination methods and adult mice with a floxed Rxfp3 gene, we deleted Rxfp3 from DG hilar neurons and assessed spatial memory performance and affective behaviors. Following infusions of an AAV(1/2)‐Cre‐IRES‐eGFP vector, Cre expression was observed in DG hilar neurons, including SST‐positive cells, andin situhybridization histochemistry for RXFP3 mRNA confirmed receptor depletion relative to levels in floxed‐RXFP3 mice infused with an AAV(1/2)‐eGFP (control) vector. RXFP3 depletion within the DG hilus impaired spatial reference memory in an appetitive T‐maze task reflected by a reduced percentage of correct choices and increased time to meet criteria, relative to control. In a continuous spontaneous alternation Y‐maze task, RXFP3‐depleted mice made fewer alternations in the first minute, suggesting impairment of spatial working memory. However, RXFP3‐depleted and control mice displayed similar locomotor activity, anxiety‐like behavior in light/dark box and elevated‐plus maze tests, and learning and long‐term memory retention in the Morris water maze. These data indicate endogenous RLN3/RXFP3 signaling can modulate hippocampal‐dependent spatial reference and working memory via effects on SST interneurons, and further our knowledge of hippocampal cognitive processing. © 2017 Wiley Periodicals, Inc.
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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) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".