Biology subjects

Medrano, E.

Publications and source records attributed to Medrano, E..

3 recordsLinked to original sources

bioRxiv2025

Genetic and Circuit Mechanisms Underlying Natural Variation in Value-Based Decision Making

How natural regulatory genetic variation shapes innate economic decision biases by modifying neural circuit structure and function remains poorly understood. Here, we trace this pathway using a value-based oviposition decision in Drosophila. While laboratory flies reject sucrose in favor of a plain substrate, a wild-caught African strain accepts sucrose. This behavioral divergence maps to three African-specific intronic SNPs in the gene pumilio (pum), encoding an RNA-binding translational repressor. These SNPs downregulate pum, derepressing its target - the voltage-gated sodium channel paralytic (para) - in a pair of GABAergic interneurons that encode option values. Increased para enhances excitability, compresses neuronal value-coding differences between sucrose and plain options, and promotes sucrose acceptance. Selectively reducing pum or overexpressing para in these neurons converts laboratory flies to the African phenotype at physiological and behavioral levels. Our findings provide a genome-to-circuit-to-behavior model, illustrating how subtle regulatory polymorphisms reshape neural computations to drive adaptive variation in economic decision-making.

neuroscience↗

bioRxiv2024

Osmolarity regulates C. elegans egg-laying behavior via parallel chemosensory and biophysical mechanisms

Animals alter their behavior in response to changes in the environment. Upon encountering hyperosmotic conditions, the nematode worm C. elegans initiates avoidance and cessation of egg-laying behavior. While the sensory pathway for osmotic avoidance is well-understood, less is known about how egg laying is inhibited. We analyzed egg-laying behavior after acute and chronic shifts to and from hyperosmotic media. Animals on 400 mM sorbitol stop laying eggs immediately but then resume [~]3 hours later, after accumulating additional eggs in the uterus. Surprisingly, the hyperosmotic cessation of egg laying did not require known osmotic avoidance signaling pathways. Acute hyperosmotic shifts in hyperosmotic-resistant mutants overproducing glycerol also blocked egg laying, but these animals resumed egg laying more quickly than similarly treated wild-type animals. These results suggest that hyperosmotic conditions disrupt a high-inside hydrostatic pressure gradient required for egg laying. Consistent with this hypothesis, animals adapted to hyperosmotic conditions laid more eggs after acute shifts back to normosmic conditions. Optogenetic stimulation of the HSN egg-laying command neurons in hyper-osmotic treated animals led to fewer and slower egg-laying events, an effect not seen following direct optogenetic stimulation of the postsynaptic vulval muscles. Hyperosmotic conditions also affected egg-laying circuit activity with the vulval muscles showing reduced Ca2+ transient amplitudes and frequency even after egg-laying resumes. Together, these results indicate that hyperosmotic conditions regulate egg-laying via two parallel mechanisms: a sensory pathway that acts to reduce HSN excitability and neurotransmitter release, and a biophysical mechanism where a hydrostatic pressure gradient reports egg accumulation in the uterus. Summary StatementWe find that hyperosmotic conditions inhibit C. elegans egg laying through both a sensory pathway and a separate biophysical pathway affecting a high-inside hydrostatic pressure gradient.

neuroscience↗

bioRxiv2022

Muscle-directed mechanosensory feedback activates egg-laying circuit activity and behavior in C. elegans

Mechanosensory feedback of internal reproductive state drives decisions about when and where to reproduce.1 For instance, stretch in the Drosophila reproductive tract produced by artificial distention or from accumulated eggs regulates the attraction to acetic acid to ensure optimal oviposition.2 How such mechanosensory feedback modulates neural circuits to coordinate reproductive behaviors is incompletely understood. We previously identified a stretch-dependent homeostat that regulates egg laying in Caenorhabditis elegans. Sterilized animals lacking eggs show reduced Ca2+ transient activity in the presynaptic HSN command motoneurons that drive egg-laying behavior while animals forced to accumulate extra eggs show dramatically increased circuit activity that restores egg laying.3 Interestingly, genetic ablation or electrical silencing of the HSNs delays, but does not abolish, the onset of egg laying3-5 with animals recovering vulval muscle Ca2+ transient activity upon egg accumulation.6 Using an acute gonad microinjection technique to mimic changes in pressure and stretch resulting from germline activity and egg accumulation, we find that injection rapidly stimulates Ca2+ activity in both neurons and muscles of the egg-laying circuit. Injection-induced vulval muscle Ca2+ activity requires L-type Ca2+ channels but is independent of presynaptic input. Conversely, injection-induced neural activity is disrupted in mutants lacking the vulval muscles, suggesting bottom-up feedback from muscles to neurons. Direct mechanical prodding activates the vulval muscles, suggesting they are the proximal targets of the stretch-dependent stimulus. Our results show that egg-laying behavior in C. elegans is regulated by a stretch-dependent homeostat that scales postsynaptic muscle responses with egg accumulation in the uterus.

neuroscience↗