Selective Routing
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BIO
OB microglia engulf LC noradrenergic axons, selectively reducing noradrenergic input to the olfactory bulb.
"We found a higher volume of NET+ immuno-signal in single microglia cells from AppNL-G-F mice compared to WT animals, as well as increased volumes of lysosomal CD68 (Fig. 3k), corroborating the increase in phagocytic activity observed in vitro."
Results, p. 5
By showing increased microglial engulfment of LC axonal material in the OB, the study demonstrates a biological gating mechanism that modulates the routing of noradrenergic signals to sensory circuits, an analogue of selective routing modules in AI systems (attention/gating) that control information flow .
Figures
Fig. 3 (p. 5)
: Confirms enhanced microglial phagocytosis of LC axons, supporting selective gating of input channels via structural removal of projections .
Limitations: Fixed-tissue and in vitro assays establish structural and functional correlates of phagocytosis; while strong, routing inferences are indirect and rely on interpreting reduced LC axon presence as reduced noradrenergic input.
Causal Control
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Genetic inhibition of microglial phagocytosis (TSPO knockout) causally rescues LC axons and olfactory behavior.
"Indeed, the lack of TSPO in AppNL-G-F mice abrogated the loss of NA axons in these animals up to an age of 6 months (Fig. 4a, b)... Importantly, the preservation of LC axons in the OB resulted in a retained ability to find the buried food pellet indistinguishable from WT animals (Fig. 4c)."
Results, p. 5
This genetic intervention provides a causal manipulation of the computation—reducing microglial phagocytosis restores noradrenergic access and behavior—mirroring causal-control tools in AI (e.g., ablations or routing edits) used to test function and mechanism .
Figures
Fig. 4 (p. 5)
: Shows that suppressing phagocytosis rescues LC axons and normalizes behavior, establishing causal control over information access in the circuit .
Limitations: Global TSPO knockout may have broader effects beyond the OB; behavioral rescue is task-specific (buried food test), and mechanistic specificity to PS-MFG-E8 signaling is supported but not exclusively proven.
Valence and Welfare
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BIO
Reduced norepinephrine release upon sensory stimulation aligns with hyposmia, indicating neuromodulatory shifts affecting sensory function.
"Functionally, the pronounced reduction of NA-release in AppNL-G-F mice upon odour stimulation can be considered a strong driver of the olfactory phenotype."
Discussion, p. 8
A neuromodulatory shift (lower NA during sensory processing) links to persistent sensory deficits, relevant to welfare/valence accounts where neuromodulators regulate salience and affect, analogous to negative-value channels in AI agents that bias perception and action .
Limitations: Statement is interpretive; while supported by imaging panels and behavior, the quote is from Discussion and does not provide exact quantitative effect sizes in-text.