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1.
Genetics ; 223(3)2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36573271

RESUMO

During nervous system development, neurons send out axons, which must navigate large distances to reach synaptic targets. Axons grow out sequentially. The early outgrowing axons, pioneers, must integrate information from various guidance cues in their environment to determine the correct direction of outgrowth. Later outgrowing follower axons can at least in part navigate by adhering to pioneer axons. In Caenorhabditis elegans, the right side of the largest longitudinal axon tract, the ventral nerve cord, is pioneered by the AVG axon. How the AVG axon navigates is only partially understood. In this study, we describe the role of two members of the IgCAM family, wrk-1 and rig-5, in AVG axon navigation. While wrk-1 and rig-5 single mutants do not show AVG navigation defects, both mutants have highly penetrant pioneer and follower navigation defects in a nid-1 mutant background. Both mutations increase the fraction of follower axons following the misguided pioneer axon. We found that wrk-1 and rig-5 act in different genetic pathways, suggesting that we identified two pioneer-independent guidance pathways used by follower axons. We assessed general locomotion, mechanosensory responsiveness, and habituation to determine whether axonal navigation defects impact nervous system function. In rig-5 nid-1 double mutants, we found no significant defects in free movement behavior; however, a subpopulation of animals shows minor changes in response duration habituation after mechanosensory stimulation. These results suggest that guidance defects of axons in the motor circuit do not necessarily lead to major movement or behavioral defects but impact more complex behavioral modulation.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Axônios/metabolismo , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Mutação , Neurônios/metabolismo
2.
Genetics ; 220(4)2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35143653

RESUMO

During nervous system development, axons navigate complex environments to reach synaptic targets. Early extending axons must interact with guidance cues in the surrounding tissue, while later extending axons can interact directly with earlier "pioneering" axons, "following" their path. In Caenorhabditis elegans, the AVG neuron pioneers the right axon tract of the ventral nerve cord. We previously found that aex-3, a rab-3 guanine nucleotide exchange factor, is essential for AVG axon navigation in a nid-1 mutant background and that aex-3 might be involved in trafficking of UNC-5, a receptor for the guidance cue UNC-6/netrin. Here, we describe a new gene in this pathway: ccd-5, a putative cdk-5 binding partner. ccd-5 mutants exhibit increased navigation defects of AVG pioneer as well as interneuron and motor neuron follower axons in a nid-1 mutant background. We show that ccd-5 acts in a pathway with cdk-5, aex-3, and unc-5. Navigation defects of follower interneuron and motoneuron axons correlate with AVG pioneer axon defects. This suggests that ccd-5 mostly affects pioneer axon navigation and that follower axon defects are largely a secondary consequence of pioneer navigation defects. To determine the consequences for nervous system function, we assessed various behavioral and movement parameters. ccd-5 single mutants have no significant movement defects, and nid-1 ccd-5 double mutants are less responsive to mechanosensory stimuli compared with nid-1 single mutants. These surprisingly minor defects indicate either a high tolerance for axon guidance defects within the motor circuit and/or an ability to maintain synaptic connections among commonly misguided axons.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Orientação de Axônios/genética , Axônios/metabolismo , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Netrinas/metabolismo , Neurônios/metabolismo , Receptores de Superfície Celular/metabolismo
3.
Curr Biol ; 31(19): R1135-R1138, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34637717

RESUMO

Many forms of synaptic plasticity are mediated by changes in the abundance, density, and expression levels of postsynaptic ionotropic receptors. A new study identifies the endogenous ligands of five 'orphan' aminergic ligand-gated ion channels in Caenorhabditis elegans, functionally characterizes these channels, and explores the role of one of them in a simple form of learning.


Assuntos
Proteínas de Caenorhabditis elegans , Conectoma , Animais , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Genoma , Neurobiologia
4.
Animals (Basel) ; 10(11)2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33203018

RESUMO

The impact that humans have on zoo animals can vary based on the species of animal, exhibit design, and individual differences in behavioral responses. We independently analyzed data from 10 never-published studies that examined the impact of zoo visitors on zoo animal behavior. Of the 16 species studied, 90.9% of the mammal species and 60.0% of the fish species demonstrated a change in at least one behavior based on zoo visitor abundance or visitor behavior (e.g., noise, solicitation of interactions from zoo animals). In addition, behavioral changes associated with zoo visitors were present in animals housed in exhibits where there was direct contact with zoo visitors, as well as in exhibits where there was indirect contact and no direct contact. Individuals often varied in their behavioral responses, and some individuals appeared to seek out interactions with visitors. Our findings demonstrate that short-term research projects can provide valuable insight into individual animal-level and species-level responses to visitor abundance and visitor behavior in the zoo setting. We recommend that behavioral assessments focus on the analysis of behaviors of individual animals whenever possible, and we recommend that exhibits provide areas that allow for animals to retreat from the public view.

5.
Int J Biochem Cell Biol ; 125: 105801, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32652305

RESUMO

Learning is critical for survival as it provides the capacity to adapt to a changing environment. At the molecular and cellular level, learning leads to alterations within neural circuits that include synaptic rewiring and synaptic plasticity. These changes are mediated by signalling molecules known as neuromodulators. One such class of neuromodulators are neuropeptides, a diverse group of short peptides that primarily act through G protein-coupled receptors. There has been substantial progress in recent years on dissecting the role of neuropeptides in learning circuits using compact yet powerful invertebrate model systems. We will focus on insights gained using the nematode Caenorhabditis elegans, with its unparalleled genetic tractability, compact nervous system of ∼300 neurons, high level of conservation with mammalian systems and amenability to a suite of behavioural analyses. Specifically, we will summarise recent discoveries in C. elegans on the role of neuropeptides in non-associative and associative learning.


Assuntos
Aprendizagem por Associação/fisiologia , Comportamento Animal/fisiologia , Caenorhabditis elegans/metabolismo , Aprendizagem/fisiologia , Neurônios/fisiologia , Neuropeptídeos/metabolismo , Transdução de Sinais/fisiologia , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Sensibilização do Sistema Nervoso Central/genética , Sensibilização do Sistema Nervoso Central/fisiologia , Habituação Psicofisiológica/genética , Habituação Psicofisiológica/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Neurônios/metabolismo , Neuropeptídeos/genética , Neurotransmissores , Transdução de Sinais/genética
6.
Bioessays ; 41(9): e1900077, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31429094

RESUMO

Recent work indicates that there are distinct response habituation mechanisms that can be recruited by different stimulation rates and that can underlie different components (e.g., the duration or speed) of a single behavioral response. These findings raise the question: why is "the simplest form of learning" so complicated mechanistically? Beyond evolutionary selection for robustness of plasticity in learning to ignore, it is proposed in this article that multiple mechanisms of habituation have evolved to streamline shifts in ongoing behavioral strategy. Then, speculations are offered regarding the implications of this reconceptualization of habituation for approaching the analysis of mechanisms of more complex forms of learning and memory.


Assuntos
Caenorhabditis elegans/fisiologia , Habituação Psicofisiológica , Nociceptividade/fisiologia , Adaptação Biológica , Animais , Comportamento , Comportamento Animal/fisiologia , Humanos , Transtornos Mentais/psicologia , Peixe-Zebra/fisiologia
7.
Curr Protoc Neurosci ; 86(1): e57, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30387915

RESUMO

In this unit, we describe an inexpensive and versatile method for optogenetic stimulation of a large population of genetically engineered Caenorhabditis elegans worms while quantitatively analyzing behavior. A custom light-emitting diode light source is used to deliver blue-light stimuli, causing direct depolarization of neurons expressing the light-gated cation channel Channelrhodopsin-2, which in turn evokes behavioral responses. The behavioral responses are recorded by a high-throughput machine vision-based tracking system, the Multi-Worm Tracker, for detailed analysis. This approach allows researchers to bypass technical obstacles to simultaneously deliver uniform stimuli to a large number of freely behaving animals and investigate the neural underpinnings of behavior. © 2018 by John Wiley & Sons, Inc.


Assuntos
Comportamento Animal/fisiologia , Caenorhabditis elegans/fisiologia , Luz , Neurônios/fisiologia , Optogenética , Animais , Modelos Animais , Optogenética/métodos
8.
Neuron ; 99(6): 1233-1246.e6, 2018 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-30146306

RESUMO

Sensitization is a simple form of behavioral plasticity by which an initial stimulus, often signaling danger, leads to increased responsiveness to subsequent stimuli. Cross-modal sensitization is an important feature of arousal in many organisms, yet its molecular and neural mechanisms are incompletely understood. Here we show that in C. elegans, aversive mechanical stimuli lead to both enhanced locomotor activity and sensitization of aversive chemosensory pathways. Both locomotor arousal and cross-modal sensitization depend on the release of FLP-20 neuropeptides from primary mechanosensory neurons and on their receptor FRPR-3. Surprisingly, the critical site of action of FRPR-3 for both sensory and locomotor arousal is RID, a single neuroendocrine cell specialized for the release of neuropeptides that responds to mechanical stimuli in a FLP-20-dependent manner. Thus, FLP-20 peptides function as an afferent arousal signal that conveys mechanosensory information to central neurons that modulate arousal and other behavioral states.


Assuntos
Nível de Alerta/fisiologia , Comportamento Animal/fisiologia , Locomoção/fisiologia , Neuropeptídeos/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Sistema Nervoso Central/metabolismo , Neurônios/fisiologia , Peptídeos/metabolismo
9.
NPJ Sci Learn ; 2: 9, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-30631455

RESUMO

Habituation is a non-associative form of learning characterized by a decremented response to repeated stimulation. It is typically framed as a process of selective attention, allowing animals to ignore irrelevant stimuli in order to free up limited cognitive resources. However, habituation can also occur to threatening and toxic stimuli, suggesting that habituation may serve other functions. Here we took advantage of a high-throughput Caenorhabditis elegans learning assay to investigate habituation to noxious stimuli. Using real-time computer vision software for automated behavioral tracking and optogenetics for controlled activation of a polymodal nociceptor, ASH, we found that neuropeptides mediated habituation and performed an RNAi screen to identify candidate receptors. Through subsequent mutant analysis and cell-type-specific gene expression, we found that pigment-dispersing factor (PDF) neuropeptides function redundantly to promote habituation via PDFR-1-mediated cAMP signaling in both neurons and muscles. Behavioral analysis during learning acquisition suggests that response habituation and sensitization of locomotion are parts of a shifting behavioral strategy orchestrated by pigment dispersing factor signaling to promote dispersal away from repeated aversive stimuli.

10.
Learn Mem ; 23(10): 495-503, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27634141

RESUMO

Habituation is a highly conserved phenomenon that remains poorly understood at the molecular level. Invertebrate model systems, like Caenorhabditis elegans, can be a powerful tool for investigating this fundamental process. Here we established a high-throughput learning assay that used real-time computer vision software for behavioral tracking and optogenetics for stimulation of the C. elegans polymodal nociceptor, ASH. Photoactivation of ASH with ChR2 elicited backward locomotion and repetitive stimulation altered aspects of the response in a manner consistent with habituation. Recording photocurrents in ASH, we observed no evidence for light adaptation of ChR2. Furthermore, we ruled out fatigue by demonstrating that sensory input from the touch cells could dishabituate the ASH avoidance circuit. Food and dopamine signaling slowed habituation downstream from ASH excitation via D1-like dopamine receptor, DOP-4. This assay allows for large-scale genetic and drug screens investigating mechanisms of nociception modulation.


Assuntos
Aprendizagem da Esquiva/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Habituação Psicofisiológica/fisiologia , Nociceptores/metabolismo , Receptores de Dopamina D2/metabolismo , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Channelrhodopsins/genética , Channelrhodopsins/metabolismo , Dopamina/metabolismo , Comportamento Alimentar/fisiologia , Processamento de Imagem Assistida por Computador , Locomoção/fisiologia , Potenciais da Membrana/fisiologia , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Atividade Motora/fisiologia , Mutação , Nociceptores/citologia , Optogenética , Técnicas de Patch-Clamp , Reconhecimento Automatizado de Padrão , Estimulação Luminosa , Receptores de Dopamina D2/genética , Sensação/fisiologia
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