Biology subjects

Ros, E.

Publications and source records attributed to Ros, E..

5 recordsLinked to original sources

bioRxiv2024

The role of olivary phase-locking oscillations in cerebellar sensorimotor adaptation

AO_SCPLOWBSTRACTC_SCPLOWThe function of the olivary nucleus is key to cerebellar adaptation as it modulates long term synaptic plasticity between parallel fibres and Purkinje cells. Here, we posit that the neural dynamics of the inferior olive (IO) network, and in particular the phase of subthreshold oscillations with respect to afferent excitatory inputs, plays a role in cerebellar sensorimotor adaptation. To test this hypothesis, we first modelled a network of 200 multi-compartment Hodgkin-Huxley IO cells, electrically coupled via anisotropic gap junctions. The model IO neural dynamics captured the properties of real olivary activity in terms of subthreshold oscillations and spike burst responses to dendritic input currents. Then, we integrated the IO network into a large-scale olivo-cerebellar model to study vestibular ocular reflex (VOR) adaptation. VOR produces eye movements contralateral to head motion to stabilise the image on the retina. Hence, studying cerebellar-dependent VOR adaptation provided insights into the functional interplay between olivary subthreshold oscillations and responses to retinal slips (i.e., image movements triggering optokinetic adaptation). Our results showed that the phase-locking of IO subthreshold oscillations to retina slip signals is a necessary condition for cerebellar VOR learning. We also found that phase-locking makes the transmission of IO spike bursts to Purkinje cells more informative with respect to the variable amplitude of retina slip errors. Finally, our results showed that the joint action of IO phase-locking and cerebellar nuclei GABAergic modulation of IO cells electrical coupling is crucial to increase the state variability of the IO network, which significantly improves cerebellar adaptation. AO_SCPLOWUTHORC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWSUMMARYC_SCPLOWThis study aims to elucidate the dual functionality of the inferior olive (IO) in cerebellar motor control, reconciling hypotheses regarding its role as either a timing or instructive signal. Specifically, we explore the role of subthreshold oscillations (STOs) within the IO, investigating their potential influence on the climbing fibres-to-Purkinje cell spike pattern responses and subsequent cerebellar adaptation, notably during the vestibulo ocular reflex. Aiming these objectives, we constructed a detailed olivary network model within a cerebellar neural network, enabling a mechanistic analysis of the functional relevance of STOs in spike burst generation, propagation, and modulation within target Purkinje cells. Our findings reveal the intricate nature of complex spike bursts triggered by climbing fibres--IO axons--into Purkinje cell dendrites, demonstrating a hybrid nature involving binary clock-like signals and graded spikelet components acting as an instructive signal.

neuroscience↗

bioRxiv2023

The spinal cord facilitates cerebellar upper limb motor learning and control; inputs from neuromusculoskeletal simulation

Complex interactions between brain regions and the spinal cord (SC) govern body motion, which is ultimately driven by muscle activation. Motor planning or learning are mainly conducted at higher brain regions, whilst the SC acts as a brain-muscle gateway and as a motor control centre providing fast reflexes and muscle activity regulation. Thus, higher brain areas need to cope with the SC as an inherent and evolutionary older part of the body dynamics. Here, we address the question of how SC dynamics affects motor learning within the cerebellum; in particular, does the SC facilitate cerebellar motor learning or constitute a biological constraint? We provide an exploratory framework by integrating biologically plausible cerebellar and SC computational models in a musculoskeletal upper limb control loop. The cerebellar model, equipped with the main form of cerebellar plasticity, provides motor adaptation; whilst the SC model implements stretch reflex and reciprocal inhibition between antagonist muscles. The resulting spino-cerebellar model is tested performing a set of upper limb motor tasks, including external perturbation studies. A cerebellar model, lacking the implemented SC model and directly controlling the simulated muscles, was also tested in the same benchmark. The performances of the spino-cerebellar and cerebellar models were then compared, thus allowing directly addressing the SC influence on cerebellar motor adaptation and learning, and on handling external motor perturbations. Performance was assessed in both joint and muscle space, and compared with kinematic and EMG recordings from healthy participants. The differences in cerebellar synaptic adaptation between both models were also studied. We conclude that the SC facilitates cerebellar motor learning; when the SC circuits are in the loop, faster convergence in motor learning is achieved with simpler cerebellar synaptic weight distributions. The SC is also found to improve robustness against external perturbations, by better reproducing and modulating muscle cocontraction patterns. SummaryAccurate motor control emerges from complex interactions between different brain areas, the spinal cord (SC), and the musculoskeletal system. These different actors contribute with distributed, integrative and complementary roles yet to be fully elucidated. To further study and hypothesise about such interactions, neuromechanical modelling and computational simulation constitute powerful tools. Here, we focus on the SC influence on motor learning in the cerebellum, an issue that has drawn little attention so far; does the SC facilitate or hinder cerebellar motor learning? To address this question, we integrate biologically plausible computational models of the cerebellum and SC, equipped with motor learning capability and fast reflex responses respectively. The resulting spino-cerebellar model is used to control a simulated musculoskeletal upper limb performing a set of motor tasks involving two degrees of freedom. Moreover, we use kinematic and EMG recordings from healthy participants to validate the model performance. The SC fast control primitives operating in muscle space are shown to facilitate cerebellar motor learning, both in terms of kinematics and synaptic adaptation. This, to the best of our knowledge, is the first time to be shown. The SC also modulates muscle cocontraction, improving the robustness against external motor perturbations.

neuroscience↗

bioRxiv2020

A computational model of homeostatic cerebellarcompensation of ageing in vestibulo-ocular reflex adaptation

The vestibulo-ocular reflex (VOR) stabilizes vision during head motion. Age-related changes of vestibular neuroanatomical properties predict a linear decay of VOR function. Nonetheless, human epidemiological data show a stable VOR function across the life span. In this study, we model cerebellum-dependent VOR adaptation to relate structural and functional changes throughout aging. We consider three neurosynaptic factors that may codetermine VOR adaptation during aging: the electrical coupling of inferior olive neurons, the intrinsic plasticity of Purkinje cell (PC) synapses, and long-term spike timing-dependent plasticity at parallel fiber - PC synapses and mossy fiber - medial vestibular nuclei synapses. Our cross-sectional aging analyses suggest that long-term plasticity acts as a global homeostatic mechanism that underpins the stable temporal profile of VOR function. The results also suggest that the intrinsic plasticity of PC synapses operates as a local homeostatic mechanism that further sustains the VOR at older ages. Importantly, the computational epidemiology approach presented in this study allows discrepancies among human cross-sectional studies to be understood in terms of interindividual variability in older individuals. Finally, our longitudinal aging simulations show that the amount of residual fibers coding for the peak and trough of the VOR cycle constitutes a predictive hallmark of VOR trajectories over a lifetime.

neuroscience↗

bioRxiv2019

genuMet: distinguish genuine untargeted metabolic features without quality control samples

MotivationLarge-scale untargeted metabolomics experiments lead to detection of thousands of novel metabolic features as well as false positive artifacts. With the incorporation of pooled QC samples and corresponding bioinformatics algorithms, those measurement artifacts can be well quality controlled. However, it is impracticable for all the studies to apply such experimental design.\n\nResultsWe introduce a post-alignment quality control method called genuMet, which is solely based on injection order of biological samples to identify potential false metabolic features. In terms of the missing pattern of metabolic signals, genuMet can reach over 95% true negative rate and 85% true positive rate with suitable parameters, compared with the algorithm utilizing pooled QC samples. genu-Met makes it possible for studies without pooled QC samples to reduce false metabolic signals and perform robust statistical analysis.\n\nAvailability and implementationgenuMet is implemented in a R package and available on https://github.com/liucaomics/genuMet under GPL-v2 license.\n\nContactLiming Liang: lliang@hsph.harvard.edu\n\nSupplementary informationSupplementary data are available at ....

bioinformatics↗

bioRxiv2018

Spike burst-pause dynamics of Purkinje cells regulate sensorimotor adaptation

Cerebellar Purkinje cells mediate accurate eye movement coordination. However, it remains unclear how oculomotor adaptation depends on the interplay between the characteristic Purkinje cell response patterns, namely tonic, bursting, and spike pauses. Here, a spiking cerebellar model assesses the role of Purkinje cell firing patterns in vestibular ocular reflex (VOR) adaptation. The model captures the cerebellar microcircuit properties and it incorporates spike-based synaptic plasticity at multiple cerebellar sites. A detailed Purkinje cell model reproduces the three spike-firing patterns that are shown to regulate the cerebellar output. Our results suggest that pauses following Purkinje complex spikes (bursts) encode transient disinhibition of targeted medial vestibular nuclei, critically gating the vestibular signals conveyed by mossy fibres. This gating mechanism accounts for early and coarse VOR acquisition, prior to the late reflex consolidation. In addition, properly timed and sized Purkinje cell bursts allow the ratio between long-term depression and potentiation (LTD/LTP) to be finely shaped at mossy fibre-medial vestibular nuclei synapses, which optimises VOR consolidation. Tonic Purkinje cell firing maintains the consolidated VOR through time. Importantly, pauses are crucial to facilitate VOR phase-reversal learning, by reshaping previously learnt synaptic weight distributions. Altogether, these results predict that Purkinje spike burst-pause dynamics are instrumental to VOR learning and reversal adaptation.\n\nAuthor SummaryCerebellar Purkinje cells regulate accurate eye movement coordination. However, it remains unclear how cerebellar-dependent oculomotor adaptation depends on the interplay between Purkinje cell characteristic response patterns: tonic, high-frequency bursting, and post-complex spike pauses. We explore the role of Purkinje spike burst-pause dynamics in VOR adaptation. A biophysical model of Purkinje cell is at the core of a spiking network model, which captures the cerebellar microcircuit properties and incorporates spike-based synaptic plasticity mechanisms at different cerebellar sites. We show that Purkinje spike burst-pause dynamics are critical for (1) gating the vestibular-motor response association during VOR acquisition; (2) mediating the LTD/LTP balance for VOR consolidation; (3) reshaping synaptic efficacy distributions for VOR phase-reversal adaptation; (4) explaining the reversal VOR gain discontinuities during sleeping.

neuroscience↗