Biology subjects

Brette, R.

Publications and source records attributed to Brette, R..

At least 19 recordsLinked to original sources

bioRxiv2026

Active control of surface immobilization in the foraging behavior of Paramecium

Paramecium is a common freshwater ciliate, a unicellular swimming eukaryote that feeds on bacteria. Since the discovery that its motility is controlled by action potentials, which earned it the nickname of "swimming neuron", many studies have documented the effect of various stimuli on its behavior, as well as their physiological basis, highlighting the richness of adaptive behavior in this unicellular organism. The logic of its autonomous behavior has received comparably less attention. For example, when Paramecium encounters a surface, it may slide or avoid it by a directional change, triggered by an action potential, or it may immobilize on the surface, a behavior often called thigmotaxis. Here we ask why and how Paramecium immobilizes on surfaces. With long term behavioral tracking, we show that this variable behavior is a component of Paramecium's foraging behavior in the presence of bacteria, where the organism alternates between exploring and stopping on surfaces to feed. This immobilization is physiologically controlled by a calcium influx. Using mutant strains, high speed imaging, particle image velocimetry and hydrodynamics simulation, we further show that surface immobilization occurs by an inhibition of locomotor cilia, while oral cilia continue beating strongly. These findings open the perspective of studying the physiological control of foraging in a unicellular organism, a complex ecologically relevant behavior potentially involving sensory processing, memory, decision making, and motor control.

microbiology↗

bioRxiv2026

Homeostatic regulation of intrinsic neuronal excitability in visual thalamic relay cells induced by brief monocular deprivation

Homeostatic plasticity of intrinsic excitability (IE) in the visual system has been essentially shown at the cortical level but whether thalamic nuclei also express homeostatic plasticity of IE is unknown. We show here that 4 days of monocular deprivation (MD) at eye opening induces a homeostatic change in IE in dorsal lateral geniculate nucleus (dLGN) neurons. Neurons recorded in the dLGN region activated by the deprived eye are more excitable than neurons recorded in the dLGN region activated by the open eye. No significant changes were observed following 7 days of MD, however. Enhanced excitability in neurons from the deprived side after 4 days of MD was associated with a reduced Kv1-dependent LTP-IE, a smaller voltage ramp, and a reduced inter-spike interval, suggesting that Kv1 channels are down-regulated in deprived dLGN neurons. Furthermore, the ankyrin G signal of the axon initial segment was larger in deprived dLGN neurons compared with open ones, indicating that Nav1 channel number also undergoes homeostatic regulation, and Kv1.1 channel signals were lower in deprived neurons compared to open ones. In addition, electrical coupling was found to be strengthened in neurons displaying enhanced IE following either brief (4 days) or long (10 days) MD. These results suggest that homeostatic and Hebbian plasticity in the dLGN share common expression mechanisms involving the regulation of Kv1 channels, Nav1 channels and electrical coupling between relay neurons.

neuroscience↗

bioRxiv2025

Single camera estimation of microswimmer depth with a convolutional network

A number of techniques have been developed to measure the three-dimensional trajectories of protists, which require special experimental setups, such as a pair of orthogonal cameras. On the other hand, machine learning techniques have been used to estimate the vertical position of spherical particles from the defocus pattern, but they require the acquisition of a labeled dataset with finely spaced vertical positions. Here we describe a simple way to make a dataset of Paramecium images labeled with vertical position from a single 5 minutes movie, based on a tilted slide setup. We used this dataset to train a simple convolutional network to estimate the vertical position of Paramecium from conventional bright field images. As an application, we show that this technique has sufficient accuracy to study the surface following behavior of Paramecium (thigmotaxis).

microbiology↗

bioRxiv2024

Theory of axo-axonic inhibition

The axon initial segment of principal cells of the cortex and hippocampus is contacted by GABAergic interneurons called chandelier cells. The anatomy, as well as alterations in neurological diseases such as epilepsy, suggest that chandelier cells exert an important inhibitory control on action potential initiation. However, their functional role remains unclear, including whether their effect is indeed inhibitory or excitatory. One reason is that there is a relative gap in electrophysiological theory about the electrical effect of axo-axonic synapses. This contribution uses resistive coupling theory, a simplification of cable theory based on the observation that the small initial segment is resistively coupled to the large cell body acting as a current sink, to fill this gap. The main theoretical finding is that a synaptic input at the proximal axon shifts the action potential threshold by an amount equal to the product of synaptic conductance, driving force at threshold, and axial axonal resistance between the soma and either the synapse or of the middle of the initial segment, whichever is closer. The theory produces quantitative estimates useful to interpret experimental observations, and supports the idea that axo-axonic cells can potentially exert powerful inhibitory control on action potential initiation. Significance statementChandelier cells form GABAergic synapses on the initial segment of pyramidal cells of the cortex and hippocampus. Despite their striking morphology and alterations in neurological diseases such as epilepsy, their functional role remains unclear. This study develops a quantitative theory to precisely assess the electrical impact of a synaptic input at the proximal axon. It shows that axo-axonic inhibition acts by shifting the action potential threshold proportionally to the synaptic conductance. This work underlines the role of chandelier cells in controlling action potential initiation and provides a quantitative tool to interpret experimental observations.

neuroscience↗

bioRxiv2023

Visual activity enhances neuronal excitability in thalamic relay neurons

The dorsal lateral geniculate nucleus (dLGN) has long been held to act as a basic relay for visual information travelling from the retina to cortical areas, but recent findings suggest a largely underestimated functional plasticity of dLGN neurons. However, the cellular mechanisms supporting this functional plasticity have not been yet explored. In particular, it remains to elucidate whether intrinsic neuronal excitability change upon visual stimuli. We show here that monocular deprivation for 10 days reduces the intrinsic excitability of dorsal LGN relay cells. Furthermore, dLGN neurons exhibit long-term potentiation of their intrinsic excitability (LTP-IE) when suprathreshold afferent retinal inputs are stimulated at 40 Hz or when spikes are induced with direct somatic current injection to reproduce patterns of retinal activity. LTP-IE is observed after eye opening and requires calcium influx mediated by L-type calcium channels. It involves activation of PKA and is expressed through the down-regulation of Kv1 potassium channels. In conclusion, our study provides the first evidence for intrinsic plasticity in dLGN relay cells, thus further pointing the role of thalamic neurons in activity-dependent visual plasticity and amblyopia.

neuroscience↗

bioRxiv2022

Interaction of the mechanosensitive microswimmer Paramecium with obstacles

In this work, we report investigations of the swimming behavior of Paramecium tetraurelia, a unicellular microorganism, in micro-engineered pools that are decorated with thousands of cylindrical pillars. Two types of contact interactions are measured, either passive scattering of Paramecium along the obstacle or avoiding reactions, characterized by an initial backward swimming upon contact, followed by a reorientation before resuming forward motion. We find that avoiding reactions are only mechanically triggered about 10% of the time. In addition, we observe that only a third of all avoiding reactions triggered by contact are instantaneous while two thirds are delayed by about 150 ms. These measurements are consistent with a simple electrophysiological model of mechanotransduction composed of a strong transient current followed by a persistent one upon prolonged contact. This is in apparent contrast with previous electrophysiological measurements where immobilized cells were stimulated with thin probes, which showed instantaneous behavioral responses and no persistent current. Our findings highlight the importance of ecologically relevant approaches to unravel the motility of mechanosensitive microorganisms in complex environments.

biophysics↗

bioRxiv2022

An electrophysiological and behavioral model of Paramecium, the "swimming neuron"

Paramecium is a large unicellular organism that swims in fresh water using cilia. When stimulated by various means (mechanically, chemically, optically, thermally), it often swims backward then turns and swims forward again in a new direction: this is called the avoiding reaction. This reaction is triggered by a calcium-based action potential. For this reason, several authors have called Paramecium the "swimming neuron". Here we present an empirically constrained model of its action potential based on electrophysiology experiments on live immobilized paramecia, together with simultaneous measurement of ciliary beating using particle image velocimetry. Using these measurements and additional behavioral measurements of free swimming, we extend the electrophysiological model by coupling calcium concentration to kinematic parameters, turning it into a swimming model. In this way, we obtain a model of autonomously behaving Paramecium. Finally, we demonstrate how the modeled organism interacts with an environment, can follow gradients and display collective behavior. This work provides a modeling basis for investigating the physiological basis of autonomous behavior of Paramecium in ecological environments. Author SummaryBehavior depends on a complex interaction between a variety of physiological processes, the body and the environment. We propose to examine this complex interaction in an organism consisting of a single excitable and motile cell, Paramecium. The behavior of Paramecium is based on trial and error: when it encounters an undesirable situation, it backs up and changes direction. This avoiding reaction is triggered by an action potential. Here we developed an empirically constrained biophysical model of Parameciums action potential, which we then coupled to its kinematics. We then demonstrate the potential of this model in investigating various types of autonomous behavior, such as obstacle avoidance, gradient-following and collective behavior.

neuroscience↗

bioRxiv2020

Neural excitability increases with axonal resistance between soma and axon initial segment

The position of the axon initial segment (AIS) is thought to play a critical role in neuronal excitability. In particular, empirical studies have found correlations between a distal shift in AIS position and a reduction of excitability. Yet, theoretical work has suggested that the neuron should become more excitable as the distance between soma and AIS is increased, because of increased electrical isolation. Specifically, resistive coupling theory predicts that the action potential (AP) threshold decreases with the logarithm of the axial resistance (Ra) between the middle of the AIS and the soma. However, no direct experimental evidence has been provided so far to support this theoretical prediction. We therefore examined how changes in Ra at the axon hillock impact the voltage threshold (Vth) of the somatic AP in L5 pyramidal neurons. Increasing Ra by mechanically pinching the axon between the soma and the AIS was found to lower the spike threshold by ~6 mV. Conversely, decreasing Ra by replacing a weakly mobile ion (gluconate) by a highly mobile ion (chloride) elevated the spike threshold. All Ra-dependent changes in spike threshold could be reproduced in a Hodgkin-Huxley compartmental model. We conclude that in L5 pyramidal neurons, excitability increases with axial resistance, and therefore with a distal shift of the AIS.

neuroscience↗

bioRxiv2020

Properties of the axial current of retinal ganglion cells at spike initiation

The action potential of most vertebrate neurons initiates in the axon initial segment (AIS), and is then transmitted to the soma where it is regenerated by somatodendritic sodium channels. For successful transmission, the AIS must produce a strong axial current, so as to depolarize the soma to the threshold for somatic regeneration. Theoretically, this axial current depends on AIS geometry and Na+ conductance density. We measured the axial current of mouse RGCs using whole-cell recordings with post-hoc AIS labeling. We found that this current is large, implying high Na+ conductance density, and carries a charge that co-varies with capacitance so as to depolarize the soma by ~30 mV. Additionally, we observed that the axial current attenuates strongly with depolarization, consistent with sodium channel inactivation, but temporally broadens so as to preserve the transmitted charge. Thus, the AIS appears to be organized so as to reliably backpropagate the axonal action potential.

neuroscience↗

bioRxiv2019

A simple device to immobilize protists for electrophysiology and microinjection

We present a simple device to mechanically immobilize motile cells such as ciliates and flagellates. It can be used in particular for intracellular electrophysiology and microinjection. A transparent filter with holes smaller than the specimen is stretched over an outlet. A flow is induced by either a peristaltic pump or a depressurized tank, mechanically entraining cells to the bottom, where they immobilize against the filter. The cells swim again freely as soon as the flow is stopped. We demonstrate the device by recording action potentials in Paramecium and injecting a fluorescent dye in the cytosol.

microbiology↗

bioRxiv2019

Theoretical relation between axon initial segment geometry and excitability

In most vertebrate neurons, action potentials are triggered at the distal end of the axon initial segment (AIS). Both position and length of the AIS vary across and within neuron types, with activity, development and pathology. What is the impact of AIS geometry on excitability? Direct empirical assessment has proven difficult because of the many potential confounding factors. Here we carried a principled theoretical analysis to answer this question. We provide a simple formula relating AIS geometry and sodium conductance density to the somatic voltage threshold. A distal shift of the AIS normally produces a (modest) increase in excitability, but we explain how this pattern can reverse if a hyperpolarizing current is present at the AIS, due to resistive coupling with the soma. This work provides a theoretical tool to assess the significance of structural AIS plasticity for electrical function.

neuroscience↗

bioRxiv2019

Axonal Na+ channels detect and transmit levels of input synchrony in local brain circuits

Sensory processing requires mechanisms of fast coincidence-detection to discriminate synchronous from asynchronous inputs. Spike-threshold adaptation enables such a discrimination but is ineffective in transmitting this information to the network. We show here that presynaptic axonal sodium channels read and transmit precise levels of input synchrony to the postsynaptic cell by modulating the presynaptic action potential (AP) amplitude. As a consequence, synaptic transmission is facilitated at cortical synapses when the presynaptic spike is produced by synchronous inputs. Using dual soma-axon recordings, imaging, and modeling, we show that this facilitation results from enhanced AP amplitude in the axon due to minimized inactivation of axonal sodium-channels. Quantifying local circuit activity and using network modeling, we found that spikes induced by synchronous inputs produced a larger effect on network activity than spikes induced by asynchronous inputs. Therefore, this input-synchrony dependent facilitation (ISF) may constitute a powerful mechanism regulating spike transmission.

neuroscience↗

bioRxiv2019

Brian 2: an intuitive and efficient neural simulator

To be maximally useful for neuroscience research, neural simulators must make it possible to define original models. This is especially important because a computational experiment might not only need descriptions of neurons and synapses, but also models of interactions with the environment (e.g. muscles), or the environment itself. To preserve high performance when defining new models, current simulators offer two options: low-level programming, or mark-up languages (and other domain specific languages). The first option requires time and expertise, is prone to errors, and contributes to problems with reproducibility and replicability. The second option has limited scope, since it can only describe the range of neural models covered by the ontology. Other aspects of a computational experiment, such as the stimulation protocol, cannot be expressed within this framework. \"Brian\" 2 is a complete rewrite of Brian that addresses this issue by using runtime code generation with a procedural equation-oriented approach. Brian 2 enables scientists to write code that is particularly simple and concise, closely matching the way they conceptualise their models, while the technique of runtime code generation automatically transforms high level descriptions of models into efficient low level code tailored to different hardware (e.g. CPU or GPU). We illustrate it with several challenging examples: a plastic model of the pyloric network of crustaceans, a closed-loop sensorimotor model, programmatic exploration of a neuron model, and an auditory model with real-time input from a microphone.

neuroscience↗

bioRxiv2018

Anticipatory adjustment of mechanical properties for motor stabilisation

External perturbation forces may compromise standing balance. The nervous system can intervene only after a delay greater than 100 ms, during which the body falls freely. With ageing, sensorimotor delays are prolonged, posing a critical threat to balance. We study a generic model of stabilisation with neural delays to understand how the organism should adapt to challenging balance conditions. The model suggests that ankle stiffness should be increased in anticipation of perturbations, for example by muscle co-contraction, so as to slow down body fall during the neural response delay. Increased ankle muscle co-contraction is indeed observed in young adults when standing in challenging balance conditions, and in older relative to young adults during normal stance. In parallel, the analysis of the model shows that increases in either stiffness or neural delay must be coordinated with decreases in spinal sensorimotor gains, otherwise the feedback itself becomes destabilizing. Accordingly, a decrease in spinal feedback is observed in challenging conditions, and with age-related increases in neural delay. These observations have been previously interpreted as indicating an increased reliance on cortical rather than spinal control of balance, despite the fact that cortical responses have a longer latency. Our analysis challenges this interpretation by showing that these observations are consistent with a functional coadaptation of spinal feedback gains to functional changes in stiffness and neural delay.\n\nAuthor summaryBeing able to stand still can be difficult when faced with an unexpected push. It takes the nervous system more than a tenth of a second to respond to such a perturbation, and during this delay the body falls under the influence of its own weight. By co-contracting their ankle muscles in anticipation of a perturbation, subjects can increase their ankle stiffness, which slows down their fall during the neural delay. Young subjects indeed adopt this strategy when they need to remain particularly still (for example when they stand in front of a cliff). Older subjects adopt this strategy even during normal standing. We present a model of standing balance that shows that this postural strategy provides partial compensation for the increase in neural delays with ageing. According to our model, increasing ankle stiffness only improves balance if it is accompanied by a decrease in sensorimotor gain. This provides a novel and functional interpretation for the decrease in spinal feedback observed during ageing, and observed in young subjects when they stand in challenging balance conditions.

neuroscience↗

bioRxiv2018

Anticipatory adjustments of posture allow elderly fallers to achieve a balance recovery performance equivalent to elderly non-fallers

BackgroundIn an important number of laboratory-based perturbation experiments, differences in the balance recovery performance of elderly fallers and non-fallers are moderate or absent. This performance may be affected by the subjects adjusting their initial posture in anticipation of the perturbation.\n\nResearch questionsDo elderly fallers and non-fallers adjust their posture in anticipation of externally-imposed perturbations in a laboratory setting, and how does this impact their balance recovery performance?\n\nMethods21 elderly non-fallers, 18 age-matched elderly fallers and 11 young adults performed both a forward waist-pull perturbation task and a Choice Stepping Reaction Time (CSRT) task. Whole-body kinematics and ground reaction forces were recorded. For each group, we evaluated the balance recovery performance in the perturbation task, change in initial center of mass (CoM) position between the CSRT and the perturbation task, and the influence of initial CoM position on task performance.\n\nResultsThe balance recovery performance of elderly fallers was equivalent to elderly non-fallers (p > 0.5 Kolmogorov-Smirnov test). All subject groups anticipated forward perturbations by shifting their CoM backward compared to the CSRT task (young: 2.1% of lower limb length, elderly non-fallers: 2.7%, elderly fallers: 2.2%, Hodges-Lehmann estimator, p < 0.001 Mann-Whitney U). This backward shift increases the probability of resisting the traction without taking a step.\n\nSignificanceThe ability to anticipate perturbations is preserved in elderly fallers and may explain their preserved balance recovery performance in laboratory-based perturbation tasks. Therefore, future studies aimed at predicting fall risk in elderly adults should carefully control for this postural strategy, by interleaving perturbations of different directions for example.

neuroscience↗

bioRxiv2018

Contribution of the axon initial segment to action potentials recorded extracellularly

Action potentials (APs) are electric phenomena that are recorded both intracellularly and extracellularly. APs are usually initiated in the short segment of the axon called the axon initial segment (AIS). It was recently proposed that at onset of an AP the soma and the AIS form a dipole. We study the extracellular signature (the extracellular action potential, EAP) generated by such a dipole. First, we demonstrate the formation of the dipole and its extracellular signature in detailed morphological models of a reconstructed pyramidal neuron. Then, we study the EAP waveform and its spatial dependence in models with axonal AP initiation and contrast it with the EAP obtained in models with somatic AP initiation. We show that in the models with axonal AP initiation the dipole forms between somatodendritic compartments and the AIS, and not between soma and dendrites as in the classical models. Soma-dendrites dipole is present only in models with somatic AP initiation. Our study has consequences for interpreting extracellular recordings of single-neuron activity and determining electrophysiological neuron types, but also for better understanding the origins of the high-frequency macroscopic electric fields recorded in the brain.\n\nNew & NoteworthyWe studied the consequences of the action potential (AP) initiation site on the extracellular signatures of APs. We show that: (1) at the time of AP initiation the action initial segment (AIS) forms a dipole with the soma, (2) the width but not (3) amplitude of the extracellular AP generated by this dipole increases with the soma-AIS distance. This may help to monitor dynamic changes in the AIS position in experimental in vivo recordings.

neuroscience↗

bioRxiv2017

Modeling neuron-glia interactions with the Brian 2 simulator

Despite compelling evidence that glial cells could crucially regulate neural network activity, the vast majority of available neural simulators ignores the possible contribution of glia to neuronal physiology. Here, we show how to model glial physiology and neuron-glia interactions in the Brian 2 simulator. Brian 2 offers facilities to explicitly describe any model in mathematical terms with limited and simple simulator-specific syntax, automatically generating high-performance code from the user-provided descriptions. The flexibility of this approach allows us to model not only networks of neurons, but also individual glial cells, electrical coupling of glial cells, and the interaction between glial cells and synapses. We therefore conclude that Brian 2 provides an ideal platform to efficiently simulate glial physiology, and specifically, the influence of astrocytes on neural activity.

neuroscience↗

bioRxiv2017

Is coding a relevant metaphor for the brain?

Short abstractI argue that the popular neural coding metaphor is often misleading. First, the \"neural code\" often spans both the experimental apparatus and the brain. Second, a neural code is information only by reference to something with a known meaning, which is not the kind of information relevant for a perceptual system. Third, the causal structure of neural codes (linear, atemporal) is incongruent with the causal structure of the brain (circular, dynamic). I conclude that a causal description of the brain cannot be based on neural codes, because spikes are more like actions than hieroglyphs.\n\nLong abstract\"Neural coding\" is a popular metaphor in neuroscience, where objective properties of the world are communicated to the brain in the form of spikes. Here I argue that this metaphor is often inappropriate and misleading. First, when neurons are said to encode experimental parameters, the neural code depends on experimental details that are not carried by the coding variable. Thus, the representational power of neural codes is much more limited than generally implied. Second, neural codes carry information only by reference to things with known meaning. In contrast, perceptual systems must build information from relations between sensory signals and actions, forming a structured internal model. Neural codes are inadequate for this purpose because they are unstructured. Third, coding variables are observables tied to the temporality of experiments, while spikes are timed actions that mediate coupling in a distributed dynamical system. The coding metaphor tries to fit the dynamic, circular and distributed causal structure of the brain into a linear chain of transformations between observables, but the two causal structures are incongruent. I conclude that the neural coding metaphor cannot provide a basis for theories of brain function, because it is incompatible with both the causal structure of the brain and the informational requirements of cognition.

neuroscience↗