Biology subjects

Squires, A.

Publications and source records attributed to Squires, A..

6 recordsLinked to original sources

bioRxiv2026

A dynamical circuit model for C. elegans chemotaxis with emergent sharp turns

With its rigorously characterized connectome, the nematode Caenorhabditis elegans is a powerful model organism to study the fundamental roles of neuronal circuits in behavior. However, despite the breadth of research, many questions remain unanswered regarding how these organisms are able to successfully navigate their environment. Here, we present a biologically grounded dynamical circuit model for the investigation of sensory-guided behavior during C. elegans chemotaxis. Our model consists of the chemosensory neuron AWA, interneurons RIM and RIA, motor neurons, including SMDs and RMDs, and body wall muscles that provide proprioceptive feedback through stretch receptors. The connectivity prioritizes functional and dynamical correspondence with the biological circuit over one-to-one anatomical fidelity. After optimization with an evolutionary algorithm, the model locomotes toward a chemical attractant, effectively capturing nematode chemotactic behavior. A key emergent property of the model that contributes to successful chemotaxis is the ability to make sharp turns, which resemble the omega turns of living nematodes. The direction and magnitude of these turns depend on the phase of the ongoing locomotory cycle. The sharp turning behavior is triggered by decreases in the concentration of the attractant. In the model, decreases in attractant concentration levels reduce AWA activity, which in turn triggers disinhibition of RIM activity and subsequent changes in RIA oscillatory activity. The ensuing coordinated changes in downstream motor neurons' activity patterns produce sharp turns, which correct the model worm's path to head toward the attractant source and, after reaching the concentration gradient peak, allow the model worm to remain in its proximity. The proposed framework and its emergent dynamics provide new insights into how circuit-level dynamics may generate key features of C. elegans chemotactic behavior, including omega-like turns. In parallel, it generates experimentally testable hypotheses about how the participating neuronal elements contribute to chemotactic behavior.

neuroscience↗

bioRxiv2026

Activity-dependent lipid droplet biogenesis and turnover regulate synaptic integrity

Lipid droplets (LDs) are conserved organelles that buffer lipid storage and stress, yet their dynamics and functions in neurons remain largely unknown. Here, we report activity-dependent dynamics of neuronal LDs, visualized by a novel, genetically encoded LD reporter (termed LipiDew), in both cultured neurons and mouse motor cortex. Using LipiDew, we found that various paradigms of neuronal activation induced predominant and transient formation of LDs in neurites. Disruption of autophagic LD degradation (lipophagy) resulted in abnormal lipid accumulation in dendritic spines and shafts, promoted recruitment of synaptic scaffolding proteins to LDs, and altered intracellular calcium kinetics in neurons. In addition, mice with neuron-specific genetic impairment of lipophagy showed motor function defects. Together, these findings identify activity-dependent LD formation and lipophagic clearance in neuronal compartments as a crucial regulatory mechanism of synaptic integrity and neuronal function.

neuroscience↗

bioRxiv2024

Whole-brain mapping in adult zebrafish and identification of a novel tank test functional connectome

Identifying general principles of brain function requires the study of structure-function relationships in a variety of species. Zebrafish have recently gained prominence as a model organism in neuroscience, yielding important insights into vertebrate brain function. Although methods have been developed for mapping neural activity in larval animals, we lack similar techniques for adult zebrafish that have the advantage of a fully developed neuroanatomy and larger behavioral repertoire. Here, we describe a pipeline built around open-source tools for whole-brain activity mapping in freely swimming adult zebrafish. Our pipeline combines recent advances in histology, microscopy, and machine learning to capture cfos activity across the entirety of the adult brain. Images captured using light-sheet microscopy are registered to the recently created adult zebrafish brain atlas (AZBA) for automated segmentation using advanced normalization tools (ANTs). We used our pipeline to measure brain activity after zebrafish were subject to the novel tank test. We found that cfos levels peaked 15 minutes following behavior and that several regions containing serotoninergic, dopaminergic, noradrenergic, and cholinergic neurons were active during exploration. Finally, we generated a novel tank test functional connectome. Functional network analysis revealed that several regions of the medial ventral telencephalon form a cohesive sub-network during exploration. We also found that the anterior portion of the parvocellular preoptic nucleus (PPa) serves as a key connection between the ventral telencephalon and many other parts of the brain. Taken together, our work enables whole-brain activity mapping in adult zebrafish for the first time while providing insight into neural basis for the novel tank test.

animal behavior and cognition↗

bioRxiv2021

Quantifying predator functional responses under field conditions reveals interactive effects of temperature and interference with sex and stage.

O_LIPredator functional responses describe predator feeding rates and are a core component of predator-prey theory. Although originally defined as the relationship between predator feeding rates and prey densities, it is now well known that predator functional responses are shaped by a multitude of factors. Unfortunately, how these factors interact with one another remains unclear, as widely used laboratory methods for measuring functional responses are generally logistically constrained to examining a few factors simultaneously. Furthermore, it is also often unclear whether laboratory derived functional responses translate to field conditions. C_LIO_LIOur goal was to apply an observational approach for measuring functional responses to understand how sex/stage differences, temperature, and predator interference interact to influence the functional response of zebra jumping spiders on midges under natural conditions. C_LIO_LIWe used field feeding surveys of jumping spiders to infer spider functional responses. We applied a Bayesian model averaging approach to estimate differences among sexes and stages of jumping spiders in their feeding rates and their dependencies on midge densities, temperature, and predator interference. C_LIO_LIWe find that females exhibit the steepest functional responses on midges, followed by juveniles, and then males, despite males being larger than juveniles. We also find that sexes and stages differ in the temperature dependence of their space clearance (aka attack) rates. We find little evidence of temperature dependence in females, whereas we find some evidence for an increase in space clearance rate at high temperatures in males and juveniles. Interference effects on feeding rates were asymmetric with little effect of interference on male feeding rates, and effects of interference on females and juveniles depending on the stage/sex from which the interference originates. C_LIO_LIOur results illustrate the multidimensional nature of functional responses in natural settings and reveal how factors influencing functional responses can interact with one another through behavior and morphology. Further studies investigating the influence of multiple mechanisms on predator functional responses under field conditions will provide an increased understanding of the drivers of predator-prey interaction strengths and their consequences for communities and ecosystems. C_LI

ecology↗

bioRxiv2021

Lipid type doping of the sponge (L3) mesophase

The polymorphism of lipid aggregates has long attracted detailed study due to the myriad factors that determine the final mesophase observed. This study is driven by the need to understand mesophase behaviour for a number of applications, such as drug delivery and membrane protein crystallography. In the case of the latter, the role of the so-called sponge (L3) mesophase has been often noted, but not extensively studied by itself. The L3 mesophase can be formed in monoolein/water systems on the addition of butanediol to water, which partitions the headgroup region of the membrane, and decreases its elastic moduli. Like cubic mesophases, it is bicontinuous, but unlike them, has no long-range translational symmetry. In our present study, we show that the formation of the L3 phase can delicately depend on the addition of dopant lipids to the mesophase. While electrostatically neutral molecules similar in shape to monoolein (DOPE, cholesterol) have little effect on the general mesophase behaviour, others (DOPC, DDM) significantly reduce the region in which it can form. Additionally, we show that by combining cholesterol with the anionic lipid DOPG, it is possible to form the largest stable L3 mesophases observed to date, with correlation lengths over 220 [A].

biophysics↗

bioRxiv2017

Single-molecule DNA unzipping reveals asymmetric modulation of the transcription factor Egr-1 by its binding site sequence and context

Most functional transcription factor (TF) binding sites deviate from their \"consensus\" recognition motif, although their sites and flanking sequences are often conserved across species. Here, we used single-molecule DNA unzipping with optical tweezers to study how Egr-1, a TF harbouring 3 zinc fingers (ZF1,ZF2 and ZF3), is modulated by the sequence and context of its functional sites in the Lhb gene promoter. We find that both the core 9 base pairs bound to Egr-1 in each of the sites, and the base pairs flanking them, modulate the affinity and structure of the protein-DNA complex. The effect of the flanking sequences is asymmetric, with a stronger effect for the sequence flanking ZF3. Characterization of the dissociation time of Egr-1 revealed that a local, mechanical perturbation of the interactions of ZF3 destabilizes the complex more effectively than a perturbation of the ZF1 interactions. Our results reveal a novel role for ZF3 in the interaction of Egr-1 with other proteins and the DNA, providing insight on the regulation of Lhb and other genes by Egr-1. Moreover, our findings reveal the potential of small changes in DNA sequence to alter transcriptional regulation, and may shed light on the organization of regulatory elements at promoters.

biophysics↗