Biology subjects

Tucker, K.

Publications and source records attributed to Tucker, K..

6 recordsLinked to original sources

bioRxiv2025

Neuroimaging and plasma biomarker differences and commonalities in Lewy body dementia subtypes

INTRODUCTIONDespite ongoing debate about whether Parkinsons disease dementia (PDD) and dementia with Lewy bodies (DLB) are separable diseases or a single Lewy body dementia (LBD) spectrum, there are limited neuroimaging investigations of differences between these conditions. METHODSWe used fixel-based diffusion MRI and plasma measures to examine white matter integrity and burden of amyloid pathology (using tau phosphorylated at theonine-217 (p-tau217) in 47 patients with DLB, 21 PDD, 29 PD and 23 age-matched controls. RESULTSWe show reduced fibre cross-section in LBD versus PD, and increased concentrations of plasma neurofilament light chain and p-tau217; with p-tau217 and fibre cross-section associated with cognition. Fibre density was reduced in PDD versus DLB, but neither plasma measures nor fibre cross-section differed between LBD subtypes. DISCUSSIONOur findings suggest differences in white matter integrity between DLB and PDD that are driven by distinct processes from those causing changes in white matter integrity in LBD compared with PD.

neuroscience↗

bioRxiv2024

Heterogeneous distribution of inhibitory inputs among motor units as a key mechanism for motor adaptations to pain

Pain significantly influences movement, yet the neural mechanisms underlying the range of observed motor adaptations remain unclear. This study combined experimental data and in silico models to investigate the contribution of inhibitory and neuromodulatory inputs to motor unit behaviour in response to nociceptive stimulation during contractions at 30% of maximal torque. Specifically, we aimed to unravel the distribution pattern of inhibitory inputs to the motor unit pool. Seventeen participants performed isometric knee extension tasks under three conditions: Control, Pain (induced by injecting hypertonic saline into the infra-patellar fat pad), and Washout. We identified large samples of motor units in the vastus lateralis (up to 53/participant) from high-density electromyographic signals, leading to three key observations. First, while motor unit discharge rates significantly decreased during Pain, a substantial proportion of motor units (14.8-24.8%) did not show this decrease and, in some cases, even exhibited an increase. Second, using complementary approaches, we found that pain did not significantly affect neuromodulation, making it unlikely to be a major contributor to the observed changes in motor unit behaviour. Third, we observed a significant reduction in the proportion of common inputs to motor units during Pain. To explore potential neurophysiological mechanisms underlying these results, we simulated the behaviour of motor unit pools with varying distribution patterns of inhibitory inputs. Our simulations support the hypothesis that a non-homogeneous distribution of inhibitory inputs, not strictly organised according to motor unit size, is a key mechanism underlying the motor response to nociceptive stimulation during moderate contraction intensity. Key pointsO_LIPain affects movement, but the neural mechanisms underlying these motor adaptations are not well defined. C_LIO_LIThe traditional view is that pain causes uniform (homogeneous) inhibition among motor units. C_LIO_LIRecent research has observed differential motor unit responses to experimental pain - some with decreased discharge rates and others with increased discharge rates. C_LIO_LICombining experimental data with modelling, we provide compelling evidence of increased inhibition that is non-uniformly distributed across motor units, regardless of their size. C_LI Legend of the abstract figureWe combined experimental data and in silico models to investigate the contribution of inhibitory and neuromodulatory inputs to motor unit behaviour in response to nociceptive stimulation during submaximal isometric contractions at 30% of maximal voluntary contraction. We identified large samples of motor units in the vastus lateralis, leading to three key observations. First, while motor unit discharge rates significantly decreased during Pain, a substantial proportion of motor units did not show this decrease and, in some cases, even exhibited an increase. Second, using complementary approaches, we found that pain did not significantly affect neuromodulation, making it unlikely to be a major contributor to the observed changes in motor unit behaviour. Third, we observed a significant reduction in the proportion of common inputs to motor units during Pain. Together with our simulations, these results provide evidence of increased inhibition that is non-uniformly distributed across motor units, regardless of their size. Ppp, pulses per second; MVC, maximal voluntary contraction.

neuroscience↗

bioRxiv2024

The volitional control of individual motor units is constrained within low-dimensional manifolds by common inputs

AbstractThe implementation of low-dimensional movement control by the central nervous system has been debated for decades. In this study, we investigated the dimensionality of the control signals received by spinal motor neurons when controlling either the ankle or knee joint torque. We first identified the low-dimensional latent factors underlying motor unit activity during torque- matched isometric contractions. Subsequently, we evaluated the extent to which motor units could be independently controlled. To this aim, we used an online control paradigm in which participants received the corresponding motor unit firing rates as visual feedback. We identified two main latent factors, regardless of the muscle group (vastus lateralis-medialis and gastrocnemius lateralis-medialis). The motor units of the gastrocnemius lateralis could be controlled largely independently from those of the gastrocnemius medialis during ankle plantarflexion. This dissociation of motor unit activity imposed similar behavior to the motor units that were not displayed in the feedback. Conversely, it was not possible to dissociate the activity of the motor units between the vastus lateralis and medialis muscles during the knee extension tasks. These results demonstrate that the number of latent factors estimated from linear dimensionality reduction algorithms does not necessarily reflect the dimensionality of volitional control of motor units. Overall, individual motor units were never controlled independently of all others but rather belonged to synergistic groups. Together, these findings provide evidence for a low-dimensional control of motor units constrained by common inputs, with notable differences between muscle groups. Significance statementIn this study, we initially examined the latent factors underlying motor unit activity in the vastii or gastrocnemii muscles during torque-matched isometric contractions. We then explored the extent to which these motor units could be controlled independently, using an online control paradigm where participants received visual information on motor unit firing rates. Although participants were able to dissociate the activity of a few motor unit pairs (from the gastrocnemius medialis and lateralis muscles), our results provide direct evidence of a low- dimensional control, constrained by common inputs, limiting flexibility in motor unit recruitment. Furthermore, we show that the number of latent factors identified by dimensionality reduction algorithms does not necessarily reflect the dimensionality of volitional control of motor units.

neuroscience↗

bioRxiv2023

I-Spin live: An open-source software based on blind-source separation for decoding the activity of spinal alpha motor neurons in real-time

Decoding the activity of individual neural cells during natural behaviours allows neuroscientists to study how the nervous system generates and controls movements. Contrary to other neural cells, the activity of spinal motor neurons can be determined non-invasively (or minimally invasively) from the decomposition of electromyographic (EMG) signals into motor unit firing activities. For some interfacing and neuro-feedback investigations, EMG decomposition needs to be performed in real-time. Here, we introduce an open-source software that performs real-time decoding of motor neurons using a blind-source separation approach for multichannel EMG signal processing. Separation vectors (motor unit filters) are optimised for each motor unit from baseline contractions and then re-applied in real-time during test contractions. In this way, the firing activity of multiple motor neurons can be provided through different forms of visual feedback. We provide a complete framework with guidelines and examples of recordings to guide researchers who aim to study movement control at the motor neuron level. We first validated the software with synthetic EMG signals generated during a range of isometric contraction patterns. We then tested the software on data collected using either surface or intramuscular electrode arrays from five lower limb muscles (gastrocnemius lateralis and medialis, vastus lateralis and medialis, and tibialis anterior). We assessed how the muscle or variation of contraction intensity between the baseline contraction and the test contraction impacted the accuracy of the real-time decomposition. This open-source software provides a set of tools for neuroscientists to design experimental paradigms where participants can receive real-time feedback on the output of the spinal cord circuits.

neuroscience↗

bioRxiv2021

Cryo-EM structures of the channelrhodopsin ChRmine in lipid nanodiscs

Microbial channelrhodopsins are light-gated ion channels widely used for optogenetic manipulation of neuronal activity. ChRmine is a bacteriorhodopsin-like cation channelrhodopsin (BCCR) more closely related to ion pump rhodopsins than other channelrhodopsins. ChRmine displays unique properties favorable for optogenetics including high light sensitivity, a red-shifted activation spectrum, cation selectivity, and large photocurrents while its slow closing kinetics impede some applications. The structural basis for ChRmine function, or that of any other BCCR, is unknown. Here, we present cryo-EM structures of ChRmine in lipid nanodiscs in apo (opsin) and retinal-bound (rhodopsin) forms. The structures reveal an unprecedented trimeric architecture with a lipid filled central pore. Large electronegative cavities on either side of the membrane facilitate high conductance and selectivity for cations over protons. The retinal binding pocket structure suggests spectral and kinetic properties could be tuned with mutations and we identify ChRmine variants with two-fold increased and ten-fold decreased closing rates. These results provide insight into structural features that generate an ultra-potent microbial opsin and provide a platform for rational engineering of channelrhodopsins with improved properties that could expand the scale, depth, and precision of optogenetic manipulations.

neuroscience↗

bioRxiv2019

Cryo-EM structure of the mitochondrial protein-import channel TOM complex from Saccharomyces cerevisiae.

Nearly all mitochondrial proteins are encoded by the nuclear genome and imported into mitochondria following synthesis on cytosolic ribosomes. These precursor proteins are translocated into mitochondria by the TOM complex, a protein-conducting channel in the mitochondrial outer membrane. Using cryo-EM, we have obtained high-resolution structures of both apo and presequence-bound core TOM complexes from Saccharomyces cerevisiae in dimeric and tetrameric forms. Dimeric TOM consists of two copies each of five proteins arranged in two-fold symmetry--Tom40, a pore-forming {beta}-barrel with an overall negatively-charged inner surface, and four auxiliary -helical transmembrane proteins. The structure suggests that presequences for mitochondrial targeting insert into the Tom40 channel mainly by electrostatic and polar interactions. The tetrameric complex is essentially a dimer of dimeric TOM, which may be capable of forming higher-order oligomers. Our study reveals the molecular organization of the TOM complex and provides new insights about the mechanism of protein translocation into mitochondria.

biochemistry↗