Pharmacologic Microglial Depletion Disrupts Breathing and Body Temperature Regulation During Torpor in 13‐lined Ground Squirrels
Bibliographic record
Abstract
Mammalian hibernation initiates dramatic changes in physiology that include large reductions in ventilation (V̇ E ), heart rate, oxygen consumption rate (V̇o 2 ), and body temperature (T b ) upon entrance into torpor, effects that reverse upon arousal. Several physiologic processes must maintain function throughout a wide range of temperatures. Recent evidence indicates that neuronal synapses loosen and retract in regions of the brain that are silenced during a torpor bout, although little is understood yet about how these connections are regulated during hibernation. Microglia, brain resident immune cells, are potential facilitators of these essential neural homeostatic activities due to their critical roles in neuronal support and synaptic strengthening and pruning. Thus, we hypothesized that microglia are required for maintaining normal ventilatory neural control during hibernation. To test this, we treated 13‐lined ground squirrels with either vehicle or colony‐stimulating factor receptor‐1 (CSF1R) antagonist, PLX3397 (80mg/kg, po), a receptor whose activation is necessary for microglial survival in the adult nervous system, and measured V̇ E , V̇o 2 , and T b throughout a torpor bout. During entrance, PLX‐treated squirrels took ~1.5 hours longer to reach their minimum torpor temperature (T b ; 12°C) compared to control animals (T b ; 9.3°C) (ambient temperature; 5‐6°C). Similarly, arousal time in microglia‐depleted animals was as much as 1 hour longer relative to controls, despite starting at a higher minimum T b . In both treatment groups, V̇o 2 during entrance fell and spiked periodically. However, in PLX‐treated animals, these spikes were much greater and more frequent. Minimum V̇o 2 in torpor was ~3 times greater in PLX‐treated animals compared to control animals. Upon arousal from torpor, V̇o 2 remained elevated, longer, in PLX‐treated squirrels. Total V̇ E tended to be elevated in PLX‐treated animals through entrance, steady state torpor, and arousal, but it was most striking during steady state torpor, where V̇ E in PLX‐treated animals was 15‐fold higher than control animals. The net result in torpor was an elevated air convection requirement, thus microglia‐depleted animals hyperventilated throughout the torpor bout. Together, these results suggest that microglia play an important regulatory role in normal ventilatory and temperature control throughout torpor and influence the rate at which animals enter into and arouse from torpor. Mechanisms whereby microglia contribute to hibernation neurophysiology are currently under 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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".