Biology subjects

Cuentas-Condori, A.

Publications and source records attributed to Cuentas-Condori, A..

6 recordsLinked to original sources

bioRxiv2026

Different forms of autophagy restrict neurite outgrowth in disparate compartments in a single neuron

Autophagy is a degradative pathway that is critical in neurons to maintain their homeostasis and to direct nervous system development. Neurons are large, highly polarized cells with distinct compartments that perform discrete functions. How an individual neuron can differentially mobilize autophagy in the axon, dendrite, and cell body is unknown. Here we interrogate the role of autophagy in the neurodevelopment of a single neuron in Caenorhabditis elegans to identify how the spatial compartmentalization of neuronal autophagy ultimately restricts neurite outgrowth in multiple neuronal compartments. However, while canonical autophagy restricts dendrite outgrowth, noncanonical forms of autophagy appear to restrain neurite outgrowth in the axon and soma. Through mutant analysis of the autophagy pathway, we identify that WIPI2-independent autophagy modulates ectopic neurite formation in the soma and that ATG9-independent autophagy regulates axon arborization. Further, we find that unrelated lipid scramblases can compensate for the loss of ATG9 in axon arborization. Our data indicate that neurons marshal both canonical and non-canonical autophagy to spatially control development of separate compartments.

neuroscience↗

bioRxiv2026

Experience-Dependent Gain Modulation Drives Thermosensory Responses in Behavior

Sensory neurons must extract behaviorally relevant features from dynamic environments while maintaining sensitivity across wide stimulus ranges. To understand how sensory encoding adapts to experience during behavior, we combine long-duration calcium imaging in freely moving C. elegans with a temperature-trajectory playback paradigm to determine how the thermosensory neuron AFD extracts behaviorally relevant sensory features during navigation. We observe that AFD functions as a leaky integrator of recently experienced temperature changes, accumulating thermal inputs over a rolling window of tens of seconds, resulting in calcium levels that represent recent temperature dynamics during runs. Importantly, we determine that AFD selectively amplifies responses to temperature changes near its learned preferred temperature. This experience-dependent gain control aligns encoding with the navigational goal, providing a mechanism for representing temperature preference within a derivative-based sensory system. A minimal mathematical model incorporating derivative detection, leaky integration, and temperature-dependent gain captures the calcium dynamics over a range of stimuli, and a simulation based on the mathematical model predicts goal-oriented locomotor strategies across stimulus regimes. Together, these findings show how gain control allows a derivative-based sensory code to represent an absolute goal and guide locomotory strategies during navigation. HighlightsO_LIAFD encodes recent temperature changes over behaviorally relevant timescales. C_LIO_LIAFD amplifies temperature-change responses within a learned temperature-centered gain window. C_LIO_LIGain control provides a mechanism for representing distance to temperature preference within the derivative-based sensory system. C_LIO_LIA mathematical model and simulation of derivative sensing, leaky integration, and gain control predicts AFD calcium responses and goal-oriented locomotory strategies across stimulus regimes. C_LI

neuroscience↗

bioRxiv2025

A Toolkit for In Vivo Mapping and Modulating Neurotransmission at Single-Cell Resolution

Understanding the organization and regulation of neurotransmission at the level of individual neurons and synapses requires tools that can track and manipulate transmitter-specific vesicles in vivo. Here, we present SynaptoTagMe, a suite of genetic tools in Caenorhabditis elegans to fluorescently label and conditionally ablate the vesicular transporters for glutamate, GABA, acetylcholine, and monoamines. Using a structure-guided approach informed by protein topology and evolutionary conservation, we engineered endogenously tagged versions for each transporter that maintain their physiological function while allowing for cell-specific, bright, and stable visualization. We also developed conditional knockout strains that enable targeted disruption of neurotransmitter synthesis or packaging in single neurons. We applied this toolkit to map co-expression of vesicular transporters across the C. elegans nervous system, revealing that over 10% of neurons exhibit co-transmission. Using the ADF sensory neuron as a case study, we demonstrate that serotonin and acetylcholine are trafficked in partially distinct vesicle pools. Our approach provides a powerful platform for mapping, monitoring, and manipulating neurotransmitter identity and use in vivo. The molecular strategies described here are likely applicable across species, offering a generalizable approach to dissect synaptic communication in vivo.

neuroscience↗

bioRxiv2022

The Epithelial Na+ Channel UNC-8 promotes an endocytic mechanism that recycles presynaptic components from old to new boutons in remodeling neurons

SummaryPresynaptic terminals are actively relocated during development to refine circuit function, but the underlying cell biological mechanisms are largely unknown. In C. elegans, the presynaptic boutons of GABAergic DD neurons are moved to new locations during early larval development. We show that developmentally regulated expression of a presynaptic Epithelial Na+ Channel (ENaC), UNC-8, promotes a Ca2+-dependent mechanism, resembling Activity-Dependent Bulk Endocytosis (ADBE), that dismantles presynaptic material for reassembly at nascent DD synapses. ADBE normally functions in highly active neurons to accelerate local recycling of synaptic vesicles. We show that DD presynaptic remodeling depends on canonical features of ADBE including elevated intracellular Ca2+, the phosphatase Calcineurin and its targets, dynamin and the F-BAR protein syndapin, and Arp2/3-driven actin polymerization. Thus, our findings suggest that a native mechanism (ADBE) for maintaining neurotransmitter release at local synapses has been repurposed, in this case, to dismantle presynaptic terminals for reassembly at new locations. HighlightsO_LIDeveloping GABAergic neurons dismantle presynaptic terminals for reassembly at new locations. C_LIO_LIThe DEG/ENaC protein, UNC-8, promotes presynaptic disassembly and recycling C_LIO_LICa2+-dependent endocytosis drives presynaptic disassembly and recycling to new boutons C_LI

neuroscience↗

bioRxiv2020

Transcriptional control of parallel-acting pathways that remove discrete presynaptic proteins in remodeling neurons

Synapses are actively dismantled to mediate circuit refinement, but the developmental pathways that regulate synaptic disassembly are largely unknown. We have previously shown that the epithelial sodium channel UNC-8 triggers an activity-dependent mechanism that drives the removal of presynaptic proteins liprin-/SYD-2, Synaptobrevin/SNB-1, RAB-3 and Endophilin/UNC-57 in remodeling GABAergic neurons in C. elegans (Miller-Fleming et al., 2016). Here, we report that the transcription factor Iroquois/IRX-1 regulates UNC-8 expression as well as an additional pathway, independent of UNC-8, that functions in parallel to dismantle functional presynaptic terminals. We show that the additional IRX-1-regulated pathway is selectively required for the removal of the presynaptic proteins, Munc13/UNC-13 and ELKS, which normally mediate synaptic vesicle fusion and neurotransmitter release. Our findings are notable because they highlight the key role of transcriptional regulation in synapse elimination and reveal parallel-acting pathways that orchestrate synaptic disassembly by removing specific active zone proteins.

neuroscience↗

bioRxiv2018

NATF (Native And Tissue-specific Fluorescence): A strategy for bright, tissue-specific GFP labeling of native proteins.

GFP labeling by genome editing can reveal the authentic location of a native protein but is frequently hampered by weak GFP signals and broad expression across a range cell types in multicellular animals. To overcome these problems, we engineered a Native And Tissue-specific Fluorescence (NATF) strategy which combines CRISPR/Cas-9 and split-GFP to yield bright, cell-specific protein labeling. We use CRISPR/Cas9 to insert a tandem array of seven copies of the GFP11 {beta}-strand (gfp11x7) at the genomic locus of each target protein. The resultant gfp11x7 knock-in strain is then crossed with separate reporter lines that express the complementing split-GFP fragment (gfp1-10) in specific cell types thus affording tissue-specific labeling of the target protein at its native level. We show that NATF reveals the otherwise undetectable intracellular location of the immunoglobulin protein, OIG-1, and demarcates a receptor auxiliary protein LEV-10 at cell-specific synaptic domains in the C. elegans nervous system.

cell biology↗