Biology subjects

Jolivet, R. B.

Publications and source records attributed to Jolivet, R. B..

5 recordsLinked to original sources

bioRxiv2023

Amyloidosis and ageing have differential effectson microglial Ca2+ activity in the mouse brain

In microglia, changes in intracellular calcium concentration ([Ca2+]i) may regulate process motility, inflammasome activation, and phagocytosis. However, while neurons and astrocytes exhibit frequent spontaneous Ca2+ activity, microglial Ca2+ signals are much rarer and poorly understood. Here, we studied [Ca2+]i changes of microglia in acute brain slices using Fluo-4-loaded cells and mice expressing GCaMP5g in microglia. Spontaneous Ca2+ transients occurred [~]5 times more frequently in individual microglial processes than in their somata. We assessed whether microglial Ca2+ responses change in Alzheimers disease (AD) using AppNL- G-F knock-in mice. Proximity to A{beta} plaques strongly affected microglial Ca2+ activity. Although spontaneous Ca2+ transients were unaffected in microglial processes, they were 5-fold more frequent in microglial somata near A{beta} plaques than in wild-type microglia. Microglia away from A{beta} plaques in AD mice showed intermediate properties for morphology and Ca2+ responses, partly resembling those of wild-type microglia. By contrast, somatic Ca2+ responses evoked by tissue damage were less intense in microglia near A{beta} plaques than in wild-type microglia, suggesting different mechanisms underlying spontaneous vs. damage-evoked Ca2+ signals. Finally, as similar processes occur in neurodegeneration and old age, we studied whether ageing affected microglial [Ca2+]i. Somatic damage-evoked Ca2+ responses were greatly reduced in microglia from old mice, as in the AD mice. In contrast to AD, however, old age did not alter the occurrence of spontaneous Ca2+ signals in microglial somata but reduced the rate of events in processes. Thus, we demonstrate distinct compartmentalised Ca2+ activity in microglia from healthy, aged and AD-like brains.

neuroscience↗

bioRxiv2020

Spike-frequency adaptation is modulated by interacting currents in an Hodgkin-Huxley-type model: Role of the Na,K-ATPase

Spike-frequency adaptation is a prominent feature of spiking neurons. Using a Hodgkin-Huxley-type model, we studied adaptation originating from the Na,K-ATPase electrogenic pump and its evolution in presence of a medium-duration calcium-dependent potassium channel. We found that the Na,K-ATPase induces spike-frequency adaptation with a time constant of up to a few seconds and interacts with the calcium-dependent potassium current through the output frequency, yielding a very typical pattern of instantaneous frequencies. Because channels responsible for spike-frequency adaptation can interact with each other, our results suggest that their meaningful time courses and parameters can be difficult to measure experimentally. To circumvent this problem, we developed a simple phenomenological model that captures the interaction between currents and allows the direct evaluation of the underlying biophysical parameters directly from the frequency vs. current curves. Finally, we found that for weak stimulations, the pump induces phasic spiking and linearly converts the stimulus amplitude in a finite number of spikes acting like an inhibitory spike-counter. Our results point to the importance of considering interacting currents involved in spike-frequency adaptation collectively rather than as isolated elements and underscore the importance of sodium as a messenger for long-term signal integration in neurons. Within this context, we propose that the Na,K-ATPase plays an important role and show how to recover relevant biological parameters from adapting channels using simple electrophysiological measurements.

neuroscience↗

bioRxiv2020

Control of microglial dynamics by Arp2/3 and the autism and schizophrenia-associated protein Cyfip1

Microglia use a highly complex and dynamic network of processes to sense and respond to their surroundings. Microglial dynamics differ throughout development and in neurological and neuropsychiatric disease, though mechanistic insight into these changes is lacking. Here we identify novel roles for regulators of the actin cytoskeleton in controlling microglial behaviour. We show that the actin branching complex Arp2/3 is critical for maintaining microglial morphology and required for surveillance but not chemotactic motility. Neuropsychiatric disease-associated Cyfip1, a core component of the WAVE regulatory complex that links Rac1 signalling to Arp2/3 activation, is highly expressed in microglia but has unknown function. We report that conditional deletion of Cyfip1 in mouse microglia reduces morphological complexity and surveillance of brain parenchyma, and increases activation state as defined by CD68 expression. Thus, altered actin-dependent microglial dynamics mediated by Cyfip1 and Arp2/3 may contribute to neuropsychiatric disease.

neuroscience↗

bioRxiv2020

Comparative performance of mutual information and transfer entropy for analyzing the balance of information flow and energy consumption at synapses

Information theory has become an essential tool of modern neuroscience. It can however be difficult to apply in experimental contexts when acquisition of very large datasets is prohibitive. Here, we compare the relative performance of two information theoretic measures, mutual information and transfer entropy, for the analysis of information flow and energetic consumption at synapses. We show that transfer entropy outperforms mutual information in terms of reliability of estimates for small datasets. However, we also show that a detailed understanding of the underlying neuronal biophysics is essential for properly interpreting the results obtained with transfer entropy. We conclude that when time and experimental conditions permit, mutual information might provide an easier to interpret alternative. Finally, we apply both measures to the study of energetic optimality of information flow at thalamic relay synapses in the visual pathway. We show that both measures recapitulate the experimental finding that these synapses are tuned to optimally balance information flowing through them with the energetic consumption associated with that synaptic and neuronal activity. Our results highlight the importance of conducting systematic computational studies prior to applying information theoretic tools to experimental data. Author summaryInformation theory has become an essential tool of modern neuroscience. It is being routinely used to evaluate how much information flows from external stimuli to various brain regions or individual neurons. It is also used to evaluate how information flows between brain regions, between neurons, across synapses, or in neural networks. Information theory offers multiple measures to do that. Two of the most popular are mutual information and transfer entropy. While these measures are related to each other, they differ in one important aspect: transfer entropy reports a directional flow of information, as mutual information does not. Here, we proceed to a systematic evaluation of their respective performances and trade-offs from the perspective of an experimentalist looking to apply these measures to binarized spike trains. We show that transfer entropy might be a better choice than mutual information when time for experimental data collection is limited, as it appears less affected by systematic biases induced by a relative lack of data. Transmission delays and integration properties of the output neuron can however complicate this picture, and we provide an example of the effect this has on both measures. We conclude that when time and experimental conditions permit, mutual information - especially when estimated using a method referred to as the direct method - might provide an easier to interpret alternative. Finally, we apply both measures in the biophysical context of evaluating the energetic optimality of information flow at thalamic relay synapses in the visual pathway. We show that both measures capture the original experimental finding that those synapses are tuned to optimally balance information flowing through them with the concomitant energetic consumption associated with that synaptic and neuronal activity.

neuroscience↗

bioRxiv2019

Myelin and nodal plasticity modulate action potential conduction in the adult mouse brain

Central nervous system myelination increases action potential conduction velocity, however, it is unclear how myelination is coordinated to ensure the temporally precise arrival of action potentials, and facilitate information processing within cortical and associative circuits. Here, we show that mature myelin remains plastic in the adult mouse brain and can undergo subtle structural modifications to influence action potential arrival times. Repetitive transcranial magnetic stimulation and spatial learning, two stimuli that modify neuronal activity, alter the length of the nodes of Ranvier and the size of the periaxonal space within active brain regions. This change in the axon-glial configuration is independent of oligodendrogenesis and tunes conduction velocity to increase the synchronicity of action potential transit.

neuroscience↗