MicroRNA (miR)-132 brain-to-body messages suppress inflammation by targeting acetylcholinesterase (AChE), but the target specificity of 3’-AChE splice variants and the signaling pathways involved remain unknown. Using surface plasmon resonance (SPR), we identified preferential miR-132 targeting of soluble AChE-R over synaptic-bound AChE-S, potentiating miR-132-mediated brain and body cholinergic suppression of pro-inflammatory cytokines. Inversely, bacterial lipopolysaccharide (LPS) reduced multiple miR-132 targets, suppressed AChE-S more than AChE-R and elevated inflammatory hallmarks. Furthermore, blockade of peripheral miR-132 by chemically protected AM132 antisense oligonucleotide elevated muscle AChE-R 10-fold over AChE-S, and cortical miRNA-sequencing demonstrated inverse brain changes by AM132 and LPS in immune-related miRs and neurotransmission and cholinergic signaling pathways. In neuromuscular junctions, AM132 co-elevated the nicotinic acetylcholine receptor and AChE, re-balancing neurotransmission and reaching mild muscle incoordination. Our findings demonstrate preferential miR-132-induced modulation of AChE-R which ignites bidirectional brain and body anti-inflammatory regulation, underscoring splice-variant miR-132 specificity as a new complexity level in inflammatory surveillance.
Rational choice theory assumes optimality in decision-making. Violations of a basic axiom of economic rationality known as “Independence of Irrelevant Alternatives” (IIA) have been demonstrated in both humans and animals and could stem from common neuronal constraints. Here we develop tests for IIA in the nematode Caenorhabditis elegans , an animal with only 302 neurons, using olfactory chemotaxis assays. We find that in most cases C. elegans make rational decisions. However, by probing multiple neuronal architectures using various choice sets, we show that violations of rationality arise when the circuit of olfactory sensory neurons is asymmetric. We further show that genetic manipulations of the asymmetry between the AWC neurons can make the worm irrational. Last, a context-dependent normalization-based model of value coding and gain control explains how particular neuronal constraints on information coding give rise to irrationality. Thus, we demonstrate that bounded rationality could arise due to basic neuronal constraints.
Rational choice theory in economics assumes optimality indecision-making.One of the basic axioms of economic rationality is "Independence of Irrelevant Alternatives" (IIA), according to which a preference ratio between two options should be unaffected by introducing additional alternatives to the choice set.Violations of IIA have been demonstrated in both humans and in various animals, and could therefore stem from common neuronal constraints. We . CC-BY-NC-ND 4.0 International license not peer-reviewed) is the author/funder. It is made available under aThe copyright holder for this preprint (which was . http://dx.doi.org/10.1101/257535 doi: bioRxiv preprint first posted online Jan. 31, 2018; used the nematode Caenorhabditis elegans, an animal with only 302 neurons and a fully mapped connectome, to examine when and why economic rationality and violations of rationality occur. We developed tests for IIA violations by characterizing the choices that C. elegans make in olfactory chemotaxis assays. In each assay, we exposed the worm to different odors that activate only specific neurons, thus involving in the choice process only defined neuronal networks, and tested whether particular neuronal architectures are prone to producing irrational choices. We found that C. elegans are capable of maintaining robust binary olfactory preferences irrespectively of the presence of a third attractive odor. However, in very specific olfactory contexts, which we term asymmetric overlaps, the preference ratio between the two odors was altered due to the addition of a third inferior odor, in a manner that violates IIA, and in certain cases can be considered "irrational" based on the economic definition of rationality. Our results suggest that different network configurations vary in their propensity to give rise to inconsistent decision making. Thus, non-optimal choices, assumed to be an outcome of high-order cognitive and mental processes, could result from much more basic attributes of neuronal activity and constrained computational mechanisms.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.