Biology subjects

Luque, N. R.

Publications and source records attributed to Luque, N. R..

3 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↗

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↗

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↗