Biology subjects

Bargmann, C. I.

Publications and source records attributed to Bargmann, C. I..

8 recordsLinked to original sources

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↗

bioRxiv2025

C. elegans interprets dietary quality through context-dependent serotonergic modulation

Animals sense their metabolic needs to guide foraging decisions using neuronal pathways that are only partly understood. Here, we systematically investigate how foraging in the nematode Caenorhabditis elegans is influenced by its bacterial diet, E. coli. By screening C. elegans behavior on 3983 E. coli knockout strains, we identified 22 E. coli metabolic mutants that are aversive to C. elegans in a long-term foraging assay. These include the global metabolic regulator CRP and genes affecting cysteine synthesis, vitamin B6 synthesis, and iron uptake. Serotonin, a neurotransmitter associated with feeding in many animals, allows C. elegans to distinguish wild-type E. coli from these "mediocre" diets through bidirectional signaling. Serotonin produced by the ADF serotonergic neurons supports attraction to wild-type E. coli with the serotonin receptor genes ser-4 and ser-5, whereas serotonin produced by the NSM serotonergic neurons differentially drives aversion to two mediocre diets through four serotonin receptor genes, ser-1, ser-7, mod-1, and lgc-50. Serotonin receptors act in multiple target neurons, including octopamine-producing neurons that suppress aversion across all diets. In addition, dopamine promotes aversion, in part by inhibiting octopaminergic neurons. These results reveal interactions between neuromodulatory circuits in the context-dependent evaluation of dietary quality.

neuroscience↗

bioRxiv2023

Evolutionary transitions from female to hermaphrodite reproduction remodel olfactory and mating-receptive behaviors

Male/hermaphrodite species have arisen multiple times from a male/female ancestral state in nematodes, providing a model to study behavioral adaptations to different reproductive strategies. Here we examined the mating behaviors of male/female (gonochoristic) Caenorhabditis species in comparison to male/hermaphrodite (androdiecious) close relatives. We find that females from two species in the Elegans group chemotax to volatile odor from males, a behavior described in only a few animal species. The females also display known mating-receptive behaviors such as sedation when male reproductive structures contact the vulva. Focusing on the male/female species C. nigoni, we show that female chemotaxis to males is limited to adult females approaching adult or near-adult males, and relies upon the AWA neuron-specific transcription factor ODR-7, as does male chemotaxis to female odor as previously shown in C. elegans. However, female receptivity during mating contact is odr-7-independent. All female behaviors are suppressed by mating, and all are absent in young hermaphrodites from the sister species C. briggsae. However, latent receptivity during mating contact can be uncovered in mutant or aged C. briggsae hermaphrodites that lack self-sperm. Young hermaphrodites from a second androdioecious species, C. tropicalis, are similarly unreceptive to males, but recover all female behaviors upon aging. These results reveal two mechanistically distinct components of the shift from female to hermaphrodite behavior: the loss of female-specific odr-7-dependent chemotaxis, and a sperm-dependent state of reduced receptivity to mating contact. The recovery of receptivity after sperm depletion has the potential to maximize hermaphrodite fitness across the lifespan. HighlightsO_LIFemale and hermaphrodite mating behaviors differ in closely related nematode species C_LIO_LIFemales are attracted to volatile male odors, but hermaphrodites are not C_LIO_LIThe same olfactory neuron pair drives female attraction to males and vice versa C_LIO_LILatent female mating behaviors are revealed in hermaphrodites that lack self-sperm C_LI

neuroscience↗

bioRxiv2022

Insulin/IGF Signaling Regulates Presynaptic Glutamate Release in Aversive Olfactory Learning

Information flow through neural circuits is continuously modified by context-dependent learning. In the nematode Caenorhabditis elegans, pairing specific odors with food deprivation results in aversion to the odor. Here we identify cell-specific mechanisms of insulin/IGF receptor signaling that integrate sensory information with food context during aversive olfactory learning. Using a conditional allele of the insulin/IGF receptor DAF-2, we show that aversive learning to butanone, an odor sensed only by the AWCON olfactory neuron, requires DAF-2 in AWCON. Learning requires an axonally-localized DAF-2c isoform and the insulin receptor substrate (IRS) protein IST-1, but is partly independent of the FoxO transcription factor DAF-16. Upon food deprivation, the unconditioned stimulus for learning, DAF-2 expression increases post-transcriptionally through an insulin- and ist-1-dependent process. Aversive learning suppresses odor-regulated glutamate release from AWCON in wild-type animals but not in ist-1 mutants, suggesting that localized insulin signaling drives presynaptic depression to generate an aversive memory.

neuroscience↗

bioRxiv2021

Context-dependent inversion of the response in a single sensory neuron type reverses olfactory preference behavior

The valence and salience of individual odorants are modulated by an animals innate preferences, learned associations, and internal state, as well as by the context of odorant presentation. The mechanisms underlying context-dependent flexibility in odor valence are not fully understood. Here we show that the behavioral response of C. elegans to bacterially-produced medium-chain alcohols switches from attraction to avoidance when presented in the background of a subset of additional attractive chemicals. This context-dependent reversal of odorant preference is driven by cell-autonomous inversion of the response to alcohols in the single AWC olfactory neuron pair. We find that while medium-chain alcohols inhibit the AWC olfactory neurons to drive attraction, these alcohols instead activate AWC to promote avoidance when presented in the background of a second AWC-sensed odorant. We show that these opposing responses are driven via engagement of different odorant-directed signal transduction pathways within AWC. Our results indicate that context-dependent recruitment of alternative intracellular signaling pathways within a single sensory neuron type conveys opposite hedonic valences, thereby providing a robust mechanism for odorant encoding and discrimination at the periphery.

neuroscience↗

bioRxiv2021

Behavioral control by depolarized and hyperpolarized states of an integrating neuron

Coordinated transitions between mutually exclusive motor states are central to behavioral decisions. During locomotion, the nematode Caenorhabditis elegans spontaneously cycles between forward runs, reversals, and turns with complex but predictable dynamics. Here we provide insight into these dynamics by demonstrating how RIM interneurons, which are active during reversals, act in two modes to stabilize both forward runs and reversals. By systematically quantifying the roles of RIM outputs during spontaneous behavior, we show that RIM lengthens reversals when depolarized through glutamate and tyramine neurotransmitters and lengthens forward runs when hyperpolarized through its gap junctions. RIM is not merely silent upon hyperpolarization: RIM gap junctions actively reinforce a hyperpolarized state of the reversal circuit. Additionally, the combined outputs of chemical synapses and gap junctions from RIM regulate forward-to-reversal transitions. Our results indicate that multiple classes of RIM synapses create behavioral inertia during spontaneous locomotion.

neuroscience↗

bioRxiv2019

Reliability of an interneuron response depends on an integrated sensory state

The central nervous system transforms sensory information into representations that are salient to the animal. Here we define the logic of this transformation in a Caenorhabditis elegans integrating interneuron. AIA interneurons receive input from multiple chemosensory neurons that detect attractive odors. We show that reliable AIA responses require the coincidence of two sensory inputs: activation of AWA olfactory neurons that are activated by attractive odors, and inhibition of one or more chemosensory neurons that are inhibited by attractive odors. AWA activates AIA through an electrical synapse, while the disinhibitory pathway acts through glutamatergic chemical synapses. The resulting AIA interneuron responses have uniform magnitude and dynamics, suggesting that AIA activation is a stereotyped response to an integrated stimulus. Our results indicate that AIA interneurons combine sensory information using AND-gate logic, requiring coordinated activity from multiple chemosensory neurons. We propose that AIA encodes positive odor valence based on an integrated sensory state.

neuroscience↗

bioRxiv2017

A natural variant and an engineered mutation in a GPCR promote DEET resistance in C. elegans

DEET (N,N-diethyl-meta-toluamide) is a synthetic chemical, identified by the United States Department of Agriculture in 1946 in a screen for repellents to protect soldiers from mosquito-borne diseases1,2. Since its discovery, DEET has become the worlds most widely used arthropod repellent3, and is effective against invertebrates separated by millions of years of evolution, including biting flies4, honeybees5, ticks6, and land leeches4,7. In insects, DEET acts on the olfactory system5,8-14 and requires the olfactory receptor co-receptor orco9,11-13, but its specific mechanism of action remains controversial. Here we show that the nematode Caenorhabditis elegans is sensitive to DEET, and use this genetically-tractable animal to study its mechanism of action. We found that DEET is not a volatile repellent, but interferes selectively with chemotaxis to a variety of attractant and repellent molecules. DEET increases pause lengths to disrupt chemotaxis to some odours but not others. In a forward genetic screen for DEET-resistant animals, we identified a single G protein-coupled receptor, str-217, which is expressed in a single pair of DEET-responsive chemosensory neurons, ADL. Misexpression of str-217 in another chemosensory neuron conferred strong responses to DEET. Both engineered str-217 mutants and a wild isolate of C. elegans carrying a deletion in str-217 are DEET-resistant. We found that DEET can interfere with behaviour by inducing an increase in average pause length during locomotion, and show that this increase in pausing requires both str-217 and ADL neurons. Finally, we demonstrated that ADL neurons are activated by DEET and that optogenetic activation of ADL increased average pause length. This is consistent with the \"confusant\" hypothesis, in which DEET is not a simple repellent but modulates multiple olfactory pathways to scramble behavioural responses12,13. Our results suggest a consistent motif for the effectiveness of DEET across widely divergent taxa: an effect on multiple chemosensory neurons to disrupt the pairing between odorant stimulus and behavioural response.

neuroscience↗