Molecular blueprints for spinal circuit modules controlling locomotor speed
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PROVIDER: PRJNA1020854 | ENA |
REPOSITORIES: ENA
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Project description:The flexibility of motor actions is ingrained in the diversity of neurons and how they are organized into functional circuit modules, yet our knowledge of the molecular underpinning of motor circuit modularity remains limited. Locomotion is a motor behavior characterized by sudden changes in speed and strength enabled by the coordinated recruitment of different motoneuron subtypes. Here we use adult zebrafish to link the molecular diversity of motoneurons and the rhythm-generating V2a interneurons with their modular circuit organization that is responsible for changes in locomotor speed. We show that the molecular diversity of motoneurons and V2a interneurons reflects their functional segregation into slow, intermediate or fast subtypes. Furthermore, we reveal shared molecular signatures between V2a interneurons and motoneurons of the three speed circuit modules. Overall, by characterizing how the molecular diversity of motoneurons and V2a interneurons relates to their function, connectivity and behavior, our study provides important insights not only into the molecular mechanisms for neuronal and circuit diversity for locomotor flexibility but also for charting circuits for motor actions in general.
2023-09-29 | GSE243993 | GEO
Project description:The flexibility of motor actions is ingrained in the diversity of neurons and how they are organized into functional circuit modules, yet our knowledge of the molecular underpinning of motor circuit modularity remains limited. Here we use adult zebrafish to link the molecular diversity of motoneurons (MNs) and the rhythm-generating V2a interneurons (INs) with the modular circuit organization that is responsible for changes in locomotor speed. We show that the molecular diversity of MNs and V2a INs reflects their functional segregation into slow, intermediate or fast subtypes. Furthermore, we reveal shared molecular signatures between V2a INs and MNs of the three speed circuit modules. Overall, by characterizing how the molecular diversity of MNs and V2a INs relates to their function, connectivity and behavior, our study provides important insights not only into the molecular mechanisms for neuronal and circuit diversity for locomotor flexibility but also for charting circuits for motor actions in general.
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Project description:Determinants of Motor Neuron Functional Subtypes Important for Locomotor Speed
| PRJNA1001940 | ENA
Project description:Locomotion requires precise control of the strength and speed of muscle contraction and is achieved by recruiting functionally-distinct subtypes of motor neurons (MNs). MNs are essential to movement and differentially susceptible in disease, but little is known about how MNs acquire functional subtype-specific features during development. Using single-cell RNA profiling in embryonic and larval zebrafish, we identify novel and conserved molecular signatures for MN functional subtypes, and identify genes expressed in both early post-mitotic and mature MNs. Assessing MN development in genetic mutants, we define a molecular program essential for MN functional subtype specification. Two evolutionarily-conserved transcription factors, Prdm16 and Mecom, are both functional subtype-specific determinants integral for fast MN development. Loss of prdm16 or mecom causes fast MNs to develop transcriptional profiles and innervation similar to slow MNs. These results reveal the molecular diversity of vertebrate axial MNs and demonstrate that functional subtypes are specified through intrinsic transcriptional codes.
2023-08-24 | GSE240026 | GEO
Project description:The functions of the Hsp70 genes were studied using a line of D. melanogaster with knockout of six these genes out of thirteen. Namely, effect of knockout of Hsp70 genes on negative geotaxis climbing (locomotor) speed and the ability to adapt to climbing training (0.5-1.5 h/day, 7 days/week, 19 days) were examined. Seven- and 23-day-old Hsp70– flies demonstrated a comparable reduction (2-fold) in locomotor speed and widespread changes in leg skeletal muscle transcriptome (RNA-seq), compared to w1118 flies. To identify the functions of genes related to decreased locomotor speed the overlapped differentially expressed genes at both time points were analyzed: the up-regulated genes encoded extracellular proteins, regulators of drug metabolism and antioxidant response, while down-regulated genes encoded regulators of carbohydrate metabolism and transmembrane proteins. Additionally, in Hsp70– flies, activation of transcription factors related to disruption of the fibril structure and heat shock response (Hsf) were predicted, using the position weight matrix approach. In the control flies, adaptation to chronic exercise training was associated mainly with gene response to a single exercise bout, while the predicted transcription factors were related to stress/immune (Hsf, NF-kB, etc.) and early gene response. In contrast, Hsp70– flies demonstrated no adaptation to training, as well as significantly impaired gene response to a single exercise bout. In conclusion, the knockout of Hsp70 genes not only reduced physical performance, but also disrupted adaptation to chronic physical training, which is associated with changes in leg skeletal muscle transcriptome and impaired gene response to a single exercise bout.
2023-08-01 | GSE239395 | GEO
Project description:Although recent vertebrate studies have revealed that different spinal networks are recruited in locomotor mode- and speed-dependent manners, it is unknown whether humans share similar neural mechanisms. Here, we tested whether speed- and mode-dependence in the recruitment of human locomotor networks exists or not by statistically extracting locomotor networks. From electromyographic activity during walking and running over a wide speed range, locomotor modules generating basic patterns of muscle activities were extracted using non-negative matrix factorization. The results showed that the number of modules changed depending on the modes and speeds. Different combinations of modules were extracted during walking and running, and at different speeds even during the same locomotor mode. These results strongly suggest that, in humans, different spinal locomotor networks are recruited while walking and running, and even in the same locomotor mode different networks are probably recruited at different speeds.
| S-EPMC5090253 | biostudies-literature
Project description:In this study we investigated the developmental dynamics of genes targeted in vivo by the transcription factor RAMOSA1, a key regulator of determinacy, and revealed potential mechanisms for repressing branches in distinct stem cell populations in developing maize inflorescences. To identify targets of RA1 and to distinguish direct vs. indirect interactions, we performed Chromatin Immunoprecipitation (ChIP)-seq and compared the results to gene expression data (RNA-seq datasets for Eveland et al., 2013, submitted). We mapped genome-wide occupancy of RA1 and showed that it differently regulates modules of target genes based on spatiotemporal context. Plants expressing complementing RA1 transgenes tagged with HA or YFP were used in parallel experiments. Ear and tassel primordia were collected and tag-specific antibodies were used to pull down RA1 bound to its target loci. Genome-wide analysis of RA1 occupancy revealed thousands of putative binding sites (i.e. peaks significantly enriched (p < 1e-05) compared to input DNA).
2013-11-27 | E-GEOD-51048 | biostudies-arrayexpress
Project description:Locomotion activates an array of sensory inputs that may help build the self-position map of the medial entorhinal cortex (MEC). In this map, speed-coding neurons are thought to dynamically update representations of the animal's position. A possible origin for the entorhinal speed signal is the mesencephalic locomotor region (MLR), which is critically involved in the activation of locomotor programs. Here, we describe, in rats, a circuit connecting the pedunculopontine tegmental nucleus (PPN) of the MLR to the MEC via the horizontal limb of the diagonal band of Broca (HDB). At each level of this pathway, locomotion speed is linearly encoded in neuronal firing rates. Optogenetic activation of PPN cells drives locomotion and modulates activity of speed-modulated neurons in HDB and MEC. Our results provide evidence for a pathway by which brainstem speed signals can reach cortical structures implicated in navigation and higher-order dynamic representations of space.
| S-EPMC7487772 | biostudies-literature
Project description:In this study we investigated the developmental dynamics of genes targeted in vivo by the transcription factor RAMOSA1, a key regulator of determinacy, and revealed potential mechanisms for repressing branches in distinct stem cell populations in developing maize inflorescences. To identify targets of RA1 and to distinguish direct vs. indirect interactions, we performed Chromatin Immunoprecipitation (ChIP)-seq and compared the results to gene expression data (RNA-seq datasets for Eveland et al., 2013, submitted). We mapped genome-wide occupancy of RA1 and showed that it differently regulates modules of target genes based on spatiotemporal context.
2013-11-27 | GSE51048 | GEO
Project description:In this study we used the maize (Zea mays) inflorescence to investigate gene networks that modulate determinacy, specifically the decision to allow branch growth. We characterized developmental transitions by associating spatiotemporal expression profiles with morphological changes resulting from genetic perturbations that disrupt steps in a pathway controlling branching. These are the RNA-seq datasets used in this study.
2013-11-27 | GSE51047 | GEO