Biology subjects

Colon-Ramos, D. A.

Publications and source records attributed to Colon-Ramos, D. A..

7 recordsLinked to original sources

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↗

bioRxiv2026

Glycolytic Specialization Shapes Neuronal Physiology and Function in vivo

Neurons perform diverse functions that impose distinct energetic demands, but how energy-metabolic pathways are matched to these functions in vivo remains unknown. Here we show that two functionally divergent sister chemosensory neurons in C. elegans, ASEL and ASER, exhibit asymmetric glycolytic flux, with ASER exhibiting high and ASEL having low levels of glycolysis. Metabolic imaging, metabolic network modeling, and electrophysiology measurements reveal that ASERs elevated glycolysis supports a hyperpolarized resting potential, low input resistance, and rapid repolarization that enable a distinct functional role compared to ASEL. Impairing glycolysis collapses these electrophysiological specializations without abolishing neuronal excitability, and selectively disrupts ASERs calcium responses while leaving ASEL largely unaffected. These findings demonstrate that neuron-specific glycolytic programs shape core biophysical properties and are required for functional identity in vivo, establishing metabolism as an active determinant of neuronal physiology.

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↗

bioRxiv2023

Local and dynamic regulation of neuronal glycolysis in vivo

Energy metabolism supports neuronal function. While it is well established that changes in energy metabolism underpin brain plasticity and function, less is known about how individual neurons modulate their metabolic states to meet varying energy demands. This is because most approaches used to examine metabolism in living organisms lack the resolution to visualize energy metabolism within individual circuits, cells, or subcellular regions. Here we adapted a biosensor for glycolysis, HYlight, for use in C. elegans to image dynamic changes in glycolysis within individual neurons and in vivo. We determined that neurons perform glycolysis cell-autonomously, and modulate glycolytic states upon energy stress. By examining glycolysis in specific neurons, we documented a neuronal energy landscape comprising three general observations: 1) glycolytic states in neurons are diverse across individual cell types; 2) for a given condition, glycolytic states within individual neurons are reproducible across animals; and 3) for varying conditions of energy stress, glycolytic states are plastic and adapt to energy demands. Through genetic analyses, we uncovered roles for regulatory enzymes and mitochondrial localization in the cellular and subcellular dynamic regulation of glycolysis. Our study demonstrates the use of a single-cell glycolytic biosensor to examine how energy metabolism is distributed across cells and coupled to dynamic states of neuronal function, and uncovers new relationships between neuronal identities and metabolic landscapes in vivo. Significance statementWhile it is generally accepted that energy metabolism underpins neuronal function, how it is distributed and dynamically regulated in different tissues of the brain to meet varying energy demands is not well understood. Here we utilized a fluorescent biosensor, HYlight, to observe glycolytic metabolism at cellular and subcellular scales in vivo. By leveraging both the stereotyped identities of individual neurons in C. elegans, and genetic tools for manipulating glycolytic metabolism, we determined that neurons perform and dynamically regulate glycolysis to match changing cellular demands for energy. Our findings support a model whereby glycolytic states should be considered distinct and related to individual neuron identities in vivo, and introduce new questions about the interconnected nature of metabolism and neuronal function.

neuroscience↗

bioRxiv2020

Cadherin Preserves Cohesion Across Involuting Tissues During C. elegans Neurulation

The internalization of the central nervous system, termed neurulation in vertebrates, is a critical step in embryogenesis. Open questions remain as to how force propels coordinated tissue movement during the process, and little is known as to how internalization happens in invertebrates. We show that in C. elegans morphogenesis, apical constriction in the retracting pharynx drives involution of the adjacent neuroectoderm. Localized HMR-1/Cadherin mediates the inter-tissue attachment, as well as within the neuroectoderm to maintain intratissue cohesion. Our results demonstrate that localized HMR-1 is capable of mediating embryo wide reorganization driven by a centrally located force generator, and indicate a non-canonical use of Cadherin on the basal side of an epithelium that may apply to vertebrate neurulation. Additionally, we highlight shared morphology and gene expression in tissues driving involution, which suggests that neuroectoderm involution in C. elegans is potentially homologous with vertebrate neurulation and thus may help elucidate the evolutionary origin of the brain.

developmental biology↗

bioRxiv2020

Structural and developmental principles of neuropil assembly in C. elegans

Neuropil is a fundamental form of tissue organization within brains1. In neuropils, densely packed neurons synaptically interconnect into precise circuit architecture2,3, yet the structural and developmental principles governing nanoscale precision in bundled neuropil assembly remain largely unknown4-6. Here we use diffusion condensation, a coarse-graining clustering algorithm7, to identify nested circuit structures within the C. elegans cerebral neuropil (called the nerve ring). We determine that the nerve ring neuropil is organized into four tightly bundled strata composed of related behavioral circuits. We demonstrate that the stratified architecture of the neuropil is a geometrical representation of the functional segregation of sensory information and motor outputs, with specific sensory organs and muscle quadrants mapping onto particular neuropil strata. We identify groups of neurons with unique morphologies that integrate information across strata and that create a sophisticated honeycomb-shaped scaffold that encases the strata within the nerve ring. We resolve the developmental sequence leading to stratified neuropil organization through the integration of lineaging and cell tracking algorithms with high resolution light-sheet microscopy, and reveal principles of cell position, migration and hierarchical outgrowth that guide neuropil organization. Our results uncover conserved design principles underlying nerve ring neuropil architecture and function, and a pioneer neuron-based, temporal progression of outgrowth that guides the hierarchical development of the layered neuropil. Our findings provide a blueprint for using structural and developmental approaches to systematically understand neuropil organization within brains.

neuroscience↗

bioRxiv2019

ADAMTS-family protease MIG-17 regulates synaptic allometry by modifying the extracellular matrix and modulating glia morphology during growth

Synapses are largely established during embryogenesis and maintained during growth. The mechanisms that regulate synaptic allometry--the maintenance of synaptic positions during growth--are largely unknown. We performed forward genetic screens in C. elegans for synaptic allometry mutants and identified mig-17, a secreted metalloprotease of the conserved ADAMTS family. Through proteomic mass spectrometry analyses, cell biological and genetic studies we determined that MIG-17 is expressed by muscle cells to modulate glia location and morphology. Glia are proximal to synapses, and the glial location and morphology determine synaptic position during growth. Mig-17 regulates synapse allometry by influencing epidermal-glia crosstalk through the regulation of basement membrane proteins, including collagen type IV, SPARC and fibulin. Our findings underscore the importance of glia location in the maintenance of synaptic allometry, and uncover a muscle-epidermal-glia signaling axis, mediated through the extracellular matrix, in the regulation of glia morphology and synaptic positions during growth.

neuroscience↗