Biology subjects

Carroll, T. J.

Publications and source records attributed to Carroll, T. J..

4 recordsLinked to original sources

bioRxiv2018

Molecular determinants of WNT9b responsiveness in nephron progenitor cells

Primed nephron progenitor cells (NPCs) appear in metanephric mesenchyme by Ell.5 and differentiate in response to the inductive WNT9b signal from the ureteric bud. However, the NPC WNT-receptor complex is unknown. We obtained M15 cells from E10.5 mesonephric mesenchyme and systematically analyzed components required for canonical WNT9b-responsiveness. When M15 cells were transfected with a ({beta}-catenin luciferase reporter plasmid, exposure to recombinant WNT9b resulted in minimal luciferase activity. We then analyzed mRNA-expression of WNT-pathway components and identified Fzdl-6 and Lrp6 transcripts but not RSPO1. When M15 cells were treated with recombinant RSPO1 the response to transfected WNT9b was augmented 4.8-fold. Co-transfection of M15 cells with Fzd5 (but no other Fzd family member) further increased the WNT9b signal to 16.8-fold and siRNA knockdown of Fzd5 reduced the signal by 52%. Knockdown of Lrp6 resulted in 60% WNT9b signal reduction. We confirmed Fzd5, Lrp6 and RSPO1 rrtRNA expression in CITED1(+) NPCs from E15.5 embryonic mouse kidney. Thus, while many WNT signaling-pathway components are present by E10.5, optimum responsiveness of Ell.5 cap mesenchyme requires that NPCs acquire RSPO1, FZD5 and LRP6.\n\nSummary StatementResponsiveness to the inductive WMT9b signal from ureteric bud is crucial for nephrogenesis. Here we analyze the molecules needed to prime nephron progenitor cells in embryonic mouse kidney.

developmental biology↗

bioRxiv2018

Unilateral movement preparation causes task-specific modulation of TMS responses in the passive, opposite limb.

Corticospinal excitability is modulated for muscles on both sides of the body during unilateral movement preparation. For the effector, there is a progressive increase in excitability, and a shift in direction of muscle twitches evoked by transcranial magnetic stimulation (TMS) toward the impending movement. By contrast, the directional characteristics of excitability changes in the opposite (passive) limb have not been fully characterized. Here we assessed how preparation of voluntary forces towards four spatially distinct visual targets with the left wrist alters muscle twitches and motor evoked potentials (MEPs) elicited by TMS of left motor cortex. MEPs were facilitated significantly more in muscles homologous to agonist rather than antagonist muscles in the active limb, from 120 ms prior to voluntary EMG onset. Thus, unilateral motor preparation has a directionally-specific influence on pathways projecting to the opposite limb that corresponds to the active muscles rather than the direction of movement in space. The directions of TMS-evoked twitches also deviated toward the impending force direction of the active limb, according to muscle-based coordinates, following the onset of voluntary EMG. The data indicate that preparation of a unilateral movement increases task-dependent excitability in ipsilateral motor cortex, or its downstream projections, that reflect the forces applied by the active limb in an intrinsic (body-centered), rather than an extrinsic (world-centered), coordinate system. The results suggest that ipsilateral motor cortical activity prior to unilateral action reflects the state of the active limb, rather than subliminal motor planning for the passive limb.

neuroscience↗

bioRxiv2016

The primary motor cortex is critical for the retention of implicit sensorimotor adaptation

Sensorimotor adaptation, or adaptation of movements to external perturbations, is thought to involve the primary motor cortex (M1). In addition to implicit error-driven remapping, explicit re-aiming strategies also contribute to sensorimotor adaptation. However, no studies to date have examined the role of M1 in implicit learning in isolation from explicit strategies. Because the application of explicit strategies requires time, it is possible to emphasise implicit learning by controlling the time available to prepare movement. Here, we examined the role of M1s role in implicit adaptation to rotated visual feedback whilst suppressing the use of explicit re-aiming strategies by limiting movement preparation times to less than 350ms. Perturbing M1 activity via single-pulse TMS during adaptation to a 30 {degrees} rotation of visual feedback did not alter the rate or extent of error compensation, but elicited poorer retention in post-adaptation trials with no perturbation. This work shows that M1 is critical in the retention of new visuomotor maps as a result of implicit adaptation to a perturbation in sensory feedback when strategic error correction processes are suppressed.\n\nHighlightsO_LIAdaptation of movements to perturbations occurs through explicit and implicit processes.\nC_LIO_LIHere, explicit strategies were suppressed by shortening movement preparation time.\nC_LIO_LIPerturbing motor cortex (M1) with TMS selectively impaired retention but not acquisition of sensorimotor adaptation.\nC_LIO_LIM1 plays a crucial role in retention of sensorimotor adaptation obtained via implicit learning.\nC_LI

neuroscience↗

bioRxiv2016

Estimating the implicit component of visuomotor rotation learning by constraining movement preparation time.

When sensory feedback is perturbed, accurate movement is restored by a combination of implicit processes and deliberate re-aiming to strategically compensate for errors. Here, we directly compare two methods used previously to dissociate implicit from explicit learning on a trial-by-trial basis: 1) asking participants to report the direction that they aim their movements, and contrasting this with the directions of the target and the movement that they actually produce, 2) manipulating movement preparation time. By instructing participants to re-aim without a sensory perturbation, we show that re-aiming is possible even with the shortest possible preparation times, particularly when targets are narrowly distributed. Nonetheless, re-aiming is effortful and comes at the cost of increased variability, so we tested whether constraining preparation time is sufficient to suppress strategic re-aiming during adaptation to visuomotor rotation with a broad target distribution. The rate and extent of error reduction under preparation time constraints were similar to estimates of implicit learning obtained from self-report without time pressure, suggesting that participants chose not to apply a re-aiming strategy to correct visual errors under time pressure. Surprisingly, participants who reported aiming directions showed less implicit learning according to an alternative measure, obtained during trials performed without visual feedback. This suggests that the process of reporting can affect the extent or persistence of implicit learning. The data extend existing evidence that restricting preparation time can suppress explicit re-aiming, and provide an estimate of implicit visuomotor rotation learning that does not require participants to report their aiming directions.\n\nNew and NoteworthyDuring sensorimotor adaptation, implicit, error-driven learning can be isolated from explicit strategy-driven re-aiming by subtracting self-reported aiming directions from movement directions, or by restricting movement preparation time. Here, we compared the two methods. Restricting preparation times did not eliminate re-aiming, but was sufficient to suppress reaiming during adaptation with widely-distributed targets. The self-report method produced a discrepancy in implicit learning estimated by subtracting aiming directions, and implicit learning measured in no-feedback trials.

neuroscience↗