Dataset Information

Control of Xenopus Tadpole Locomotion via Selective Expression of Ih in Excitatory Interneurons.

ABSTRACT: Locomotion relies on the coordinated activity of rhythmic neurons in the hindbrain and spinal cord and depends critically on the intrinsic properties of excitatory interneurons. Therefore, understanding how ion channels sculpt the properties of these interneurons, and the consequences for circuit function and behavior, is an important task. The hyperpolarization-activated cation current, Ih, is known to play important roles in shaping neuronal properties and for rhythm generation in many neuronal networks. We show in stage 42 Xenopus laevis frog tadpoles that Ih is strongly expressed only in excitatory descending interneurons (dINs), an important ipsilaterally projecting population that drives swimming activity. The voltage-dependent HCN channel blocker ZD7288 completely abolished a prominent depolarizing sag potential in response to hyperpolarization, the hallmark of Ih, and hyperpolarized dINs. ZD7288 also affected dIN post-inhibitory rebound firing, upon which locomotor rhythm generation relies, and disrupted locomotor output. Block of Ih also unmasked an activity-dependent ultraslow afterhyperpolarization (usAHP) in dINs following swimming, mediated by a dynamic Na/K pump current. This usAHP, unmasked in dINs by ZD7288, resulted in suprathreshold stimuli failing to evoke swimming at short inter-swim intervals, indicating an important role for Ih in maintaining swim generation capacity and in setting the post-swim refractory period of the network. Collectively, our data suggest that the selective expression of Ih in dINs determines specific dIN properties that are important for rhythm generation and counteracts an activity-dependent usAHP to ensure that dINs can maintain coordinated swimming over a wide range of inter-swim intervals.

SUBMITTER: Picton LD

PROVIDER: S-EPMC6303192 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Control of Xenopus Tadpole Locomotion via Selective Expression of Ih in Excitatory Interneurons.

Picton Laurence D LD Sillar Keith T KT Zhang Hong-Yan HY

Current biology : CB 20181129 24

Locomotion relies on the coordinated activity of rhythmic neurons in the hindbrain and spinal cord and depends critically on the intrinsic properties of excitatory interneurons. Therefore, understanding how ion channels sculpt the properties of these interneurons, and the consequences for circuit function and behavior, is an important task. The hyperpolarization-activated cation current, Ih, is known to play important roles in shaping neuronal properties and for rhythm generation in many neurona ...[more]

PMID: 30503615

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Project description:The global amphibian declines are compounded by infections with members of the Ranavirus genus such as Frog Virus 3 (FV3). Premetamorphic anuran amphibians are believed to be significantly more susceptible to FV3 while this pathogen targets the kidneys of both pre- and postmetamorphic animals. Paradoxically, FV3-challenged Xenopus laevis tadpoles exhibit lower kidney viral loads than adult frogs. Presently, we demonstrate that X. laevis tadpoles are intrinsically more resistant to FV3 kidney infections than cohort-matched metamorphic and postmetamorphic froglets and that this resistance appears to be epigenetically conferred by endogenous retroviruses (ERVs). Using a X. laevis kidney-derived cell line, we show that enhancing ERV gene expression activates cellular double-stranded RNA-sensing pathways, resulting in elevated mRNA levels of antiviral interferon (IFN) cytokines and thus greater anti-FV3 protection. Finally, our results indicate that large esterase-positive myeloid-lineage cells, rather than renal cells, are responsible for the elevated ERV/IFN axis seen in the tadpole kidneys. This conclusion is supported by our observation that CRISPR-Cas9 ablation of colony-stimulating factor-3 results in abolished homing of these myeloid cells to tadpole kidneys, concurrent with significantly abolished tadpole kidney expression of both ERVs and IFNs. We believe that the manuscript marks an important step forward in understanding the mechanisms controlling amphibian antiviral defenses and thus susceptibility and resistance to pathogens like FV3. IMPORTANCE Global amphibian biodiversity is being challenged by pathogens like the Frog Virus 3 (FV3) ranavirus, underlining the need to gain a greater understanding of amphibian antiviral defenses. While it was previously believed that anuran (frog/toad) amphibian tadpoles are more susceptible to FV3, we demonstrated that tadpoles are in fact more resistant to this virus than metamorphic and postmetamorphic froglets. We showed that this resistance is conferred by large myeloid cells within the tadpole kidneys (central FV3 target), which possess an elevated expression of endogenous retroviruses (ERVs). In turn, these ERVs activate cellular double-stranded RNA-sensing pathways, resulting in a greater expression of antiviral interferon cytokines, thereby offering the observed anti-FV3 protection.

Project description:Organ regenerative ability depends on the animal species and the developmental stage. The molecular bases for variable organ regenerative ability, however, remain unknown. Previous studies have identified genes preferentially expressed in the blastema tissues in various animals, but transcriptome analysis of the isolated proliferating blastema cells has not yet been reported. In the present study, we used RNA-sequencing analysis to analyze the gene expression profile of isolated proliferating blastema cells of regenerating Xenopus laevis tadpole tails. We used flow cytometry to isolate proliferating cells, and non-proliferating blastema cells, from regenerating tadpole tails as well as proliferating tail bud cells from tail bud embryos, the latter two of which were used as control cells, based on their DNA content. Among the 28 candidate genes identified by RNA-sequencing analysis, quantitative reverse transcription-polymerase chain reaction identified 10 genes whose expression was enriched in regenerating tadpole tails compared with non-regenerating tadpole tails or tails from the tail bud embryos. Among them, whole mount in situ hybridization revealed that chromosome segregation 1-like and interleukin 11 were expressed in the broad area of the tail blastema, while brevican, lysyl oxidase, and keratin 18 were mainly expressed in the notochord bud in regenerating tails. We further combined whole mount in situ hybridization with immunohistochemistry for the incorporated 5-bromo-2-deoxyuridine to confirm that keratin 18 and interleukin 11 were expressed in the proliferating tail blastema cells. Based on the proposed functions of their homologs in other animal species, these genes might have roles in the extracellular matrix formation in the notochord bud (brevican and lysyl oxidase), cell proliferation (chromosome segregation 1-like and keratin 18), and in the maintenance of the differentiation ability of proliferating blastema cells (interleukin 11) in regenerating tadpole tails.

Dataset Information

Control of Xenopus Tadpole Locomotion via Selective Expression of Ih in Excitatory Interneurons.

Publications

Control of Xenopus Tadpole Locomotion via Selective Expression of Ih in Excitatory Interneurons.

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