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1.
Neuron ; 112(9): 1473-1486.e6, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38447577

RESUMEN

Phasic (fast) and tonic (sustained) inhibition of γ-aminobutyric acid (GABA) are fundamental for regulating day-to-day activities, neuronal excitability, and plasticity. However, the mechanisms and physiological functions of glial GABA transductions remain poorly understood. Here, we report that the AMsh glia in Caenorhabditis elegans exhibit both phasic and tonic GABAergic signaling, which distinctively regulate olfactory adaptation and neuronal aging. Through genetic screening, we find that GABA permeates through bestrophin-9/-13/-14 anion channels from AMsh glia, which primarily activate the metabolic GABAB receptor GBB-1 in the neighboring ASH sensory neurons. This tonic action of glial GABA regulates the age-associated changes of ASH neurons and olfactory responses via a conserved signaling pathway, inducing neuroprotection. In addition, the calcium-evoked, vesicular glial GABA release acts upon the ionotropic GABAA receptor LGC-38 in ASH neurons to regulate olfactory adaptation. These findings underscore the fundamental significance of glial GABA in maintaining healthy aging and neuronal stability.


Asunto(s)
Adaptación Fisiológica , Caenorhabditis elegans , Neuroglía , Ácido gamma-Aminobutírico , Animales , Ácido gamma-Aminobutírico/metabolismo , Neuroglía/metabolismo , Neuroglía/fisiología , Adaptación Fisiológica/fisiología , Olfato/fisiología , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Transducción de Señal/fisiología , Senescencia Celular/fisiología , Neuronas Receptoras Olfatorias/fisiología , Neuronas Receptoras Olfatorias/metabolismo , Envejecimiento/fisiología , Envejecimiento/metabolismo , Receptores de GABA-A/metabolismo
2.
Front Mol Neurosci ; 15: 907064, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35782381

RESUMEN

Calcium channelopathies have been strongly linked to cardiovascular, muscular, neurological and psychiatric disorders. The voltage-gated calcium channels (VGCC) are vital transducers of membrane potential changes to facilitate the dynamics of calcium ions and release of neurotransmitter. Whether these channels function in the glial cell to mediate calcium variations and regulate behavioral outputs, is poorly understood. Our results showed that odorant and mechanical stimuli evoked robust calcium increases in the amphid sheath (AMsh) glia from C. elegans, which were largely dependent on the L-Type VGCC EGL-19. Moreover, EGL-19 modulates the morphologies of both ASH sensory neurons and AMsh glia. Tissue-specific knock-down of EGL-19 in AMsh glia regulated sensory adaptability of ASH neurons and promoted olfactory adaptation. Our results reveal a novel role of glial L-Type VGCC EGL-19 on olfaction, lead to improved understanding of the functions of VGCCs in sensory transduction.

3.
Nat Aging ; 1(11): 991-1001, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-37118342

RESUMEN

To identify candidate bacteria associated with aging, we performed fecal microbiota sequencing in young, middle-aged and older adults, and found lower Bifidobacterium adolescentis abundance in older individuals aged ≥60 years. Dietary supplementation of B. adolescentis improved osteoporosis and neurodegeneration in a mouse model of premature aging (Terc-/-) and increased healthspan and lifespan in Drosophila melanogaster and Caenorhabditis elegans. B. adolescentis supplementation increased the activity of the catalase (CAT) enzyme in skeletal muscle and brain tissue from Terc-/- mice, and suppressed cellular senescence in mouse embryonic fibroblasts. Transgenic deletion of catalase (ctl-2) in C. elegans abolished the effects of B. adolescentis on the lifespan and healthspan. B. adolescentis feeding also led to changes in oxidative stress-associated metabolites in Terc-/- mouse feces. These results suggest a role for B. adolescentis in improving the healthspan and lifespan through the regulation of CAT activity and host metabolism.


Asunto(s)
Bifidobacterium adolescentis , Animales , Ratones , Longevidad , Caenorhabditis elegans/genética , Catalasa , Drosophila melanogaster , Fibroblastos
4.
Neurosci Bull ; 37(5): 611-622, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33555565

RESUMEN

Sensory modalities are important for survival but the molecular mechanisms remain challenging due to the polymodal functionality of sensory neurons. Here, we report the C. elegans outer labial lateral (OLL) sensilla sensory neurons respond to touch and cold. Mechanosensation of OLL neurons resulted in cell-autonomous mechanically-evoked Ca2+ transients and rapidly-adapting mechanoreceptor currents with a very short latency. Mechanotransduction of OLL neurons might be carried by a novel Na+ conductance channel, which is insensitive to amiloride. The bona fide mechano-gated Na+-selective degenerin/epithelial Na+ channels, TRP-4, TMC, and Piezo proteins are not involved in this mechanosensation. Interestingly, OLL neurons also mediated cold but not warm responses in a cell-autonomous manner. We further showed that the cold response of OLL neurons is not mediated by the cold receptor TRPA-1 or the temperature-sensitive glutamate receptor GLR-3. Thus, we propose the polymodal functionality of OLL neurons in mechanosensation and cold sensation.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Proteínas de Caenorhabditis elegans/genética , Mecanotransducción Celular , Células Receptoras Sensoriales , Tacto
5.
Neuron ; 108(4): 707-721.e8, 2020 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-32970991

RESUMEN

Glia are typically considered as supporting cells for neural development and synaptic transmission. Here, we report an active role of a glia in olfactory transduction. As a polymodal sensory neuron in C. elegans, the ASH neuron is previously known to detect multiple aversive odorants. We reveal that the AMsh glia, a sheath for multiple sensory neurons including ASH, cell-autonomously respond to aversive odorants via G-protein-coupled receptors (GPCRs) distinct from those in ASH. Upon activation, the AMsh glia suppress aversive odorant-triggered avoidance and promote olfactory adaptation by inhibiting the ASH neuron via GABA signaling. Thus, we propose a novel two-receptor model where the glia and sensory neuron jointly mediate adaptive olfaction. Our study reveals a non-canonical function of glial cells in olfactory transduction, which may provide new insights into the glia-like supporting cells in mammalian sensory procession.


Asunto(s)
Neuroglía/fisiología , Odorantes/análisis , Neuronas Receptoras Olfatorias/fisiología , Receptores Odorantes/fisiología , Olfato/fisiología , Animales , Animales Modificados Genéticamente , Neuronas GABAérgicas/fisiología , Mutación , Inhibición Neural/fisiología , Transducción de Señal
6.
Nat Commun ; 9(1): 4311, 2018 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-30333484

RESUMEN

How neurons are capable of decoding stimulus intensity and translate this information into complex behavioral outputs is poorly defined. Here, we demonstrate that the C. elegans interneuron AIB regulates two types of behaviors: reversal initiation and feeding suppression in response to different concentrations of quinine. Low concentrations of quinine are decoded in AIB by a low-threshold, fast-inactivation glutamate receptor GLR-1 and translated into reversal initiation. In contrast, high concentrations of quinine are decoded by a high-threshold, slow-inactivation glutamate receptor GLR-5 in AIB. After activation, GLR-5 evokes sustained Ca2+ release from the inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ stores and triggers neuropeptide secretion, which in turn activates the downstream neuron RIM and inhibits feeding. Our results reveal that distinct signal patterns in a single interneuron AIB can encode differential behavioral outputs depending on the stimulus intensity, thus highlighting the importance of functional mapping of information propagation at the single-neuron level during connectome construction.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiología , Conducta Alimentaria/fisiología , Interneuronas/fisiología , Receptores AMPA/metabolismo , Animales , Señalización del Calcio , Proteínas Portadoras/metabolismo , Quinina , Células Receptoras Sensoriales/fisiología , Umbral Sensorial
7.
Neuron ; 97(3): 571-585.e5, 2018 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-29395910

RESUMEN

Membrane excitability is a fundamentally important feature for all excitable cells including both neurons and muscle cells. However, the background depolarizing conductances in excitable cells, especially in muscle cells, are not well characterized. Although mutations in transmembrane channel-like (TMC) proteins TMC1 and TMC2 cause deafness and vestibular defects in mammals, their precise action modes are elusive. Here, we discover that both TMC-1 and TMC-2 are required for normal egg laying in C. elegans. Mutations in these TMC proteins cause membrane hyperpolarization and disrupt the rhythmic calcium activities in both neurons and muscles involved in egg laying. Mechanistically, TMC proteins enhance membrane depolarization through background leak currents and ectopic expression of both C. elegans and mammalian TMC proteins results in membrane depolarization. Therefore, we have identified an unexpected role of TMC proteins in modulating membrane excitability. Our results may provide mechanistic insights into the functions of TMC proteins in hearing loss and other diseases.


Asunto(s)
Proteínas de Caenorhabditis elegans/fisiología , Canales Iónicos/fisiología , Potenciales de la Membrana , Músculos/fisiología , Neuronas/fisiología , Conducta Sexual Animal , Animales , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/metabolismo , Canales Iónicos/metabolismo , Neuronas/metabolismo
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