Biology subjects

Gorski, T.

Publications and source records attributed to Gorski, T..

5 recordsLinked to original sources

bioRxiv2022

MME+ fibro-adipogenic progenitors are the dominant adipogenic population during fatty infiltration in human skeletal muscle

Summary/Abstract Fatty infiltration, the ectopic deposition of adipose tissue within skeletal muscle, is mediated via the adipogenic differentiation of fibro-adipogenic progenitors (FAPs). We used single-nuclei and single- cell RNA sequencing to characterize FAP heterogeneity in patients with fatty infiltration. We identified an MME+ FAP subpopulation which, based on ex vivo characterization as well as transplantation experiments, exhibits high adipogenic potential. MME+ FAPs are characterized by low activity of WNT, known to control adipogenic commitment, and are refractory to the inhibitory role of WNT activators. Using preclinical models for muscle damage versus fatty infiltration, we show that many MME+ FAPs undergo apoptosis during muscle regeneration and differentiate into adipocytes under pathological conditions, leading to their depletion. Finally, we utilized the varying fat infiltration levels in human hip muscles to show the depletion of MME+ FAPs in fatty infiltrated human muscle. Altogether, we have identified the dominant adipogenic FAP subpopulation in skeletal muscle.

cell biology↗

bioRxiv2020

Exercise promotes satellite cell contribution to myofibers in a load-dependent manner

Satellite cells (SCs) are required for muscle repair following injury and are involved in muscle remodeling upon muscular contractions. Exercise stimulates SC accumulation and myonuclear accretion. To what extent exercise training at different mechanical loads drive SC contribution to myonuclei however is unknown. By performing SC fate tracing experiments, we show that 8-weeks of voluntary wheel running increased SC contribution to myonuclei in mouse plantar flexor muscles in a load-dependent but fiber type-independent manner. Increased SC fusion however was not exclusively linked to muscle hypertrophy as wheel running without external load substantially increased SC fusion in the absence of fiber hypertrophy. Due to nuclear propagation, nuclear fluorescent fate tracing mouse models were inadequate to quantify SC contribution to myonuclei. Ultimately, by performing fate tracing at the DNA level, we show that SC contribution mirrors myonuclear accretion during exercise. Collectively, these findings provide direct evidence that mechanical load during exercise independently promotes SC contribution to existing myofibers.

cell biology↗

bioRxiv2019

Conductance-based Adaptive Exponential integrate-and-fire model

The intrinsic electrophysiological properties of single neurons can be described by a broad spectrum of models, from the most realistic Hodgkin-Huxley type models with numerous detailed mechanisms to the phenomeno-logical models. The Adaptive Exponential integrate-and-fire (AdEx) model has emerged as a convenient "middle-ground" model. With a low computational cost, but keeping biophysical interpretation of the parameters, it has been extensively used for simulations of large neural networks. However, because of its current-based adaptation, it can generate unrealistic behaviors. We show the limitations of the AdEx model and to avoid them, we introduce the Conductance-based Adaptive Exponential integrate-and-fire model (CAdEx). We give an analysis of the dynamics of the CAdEx model and show the variety of firing patterns it can produce. We propose the CAdEx model as a richer alternative to perform network simulations with simplified models reproducing neuronal intrinsic properties.

neuroscience↗

bioRxiv2018

Two types of slow waves in anesthetized and sleeping brains

Sleep slow waves are known to participate in memory consolidation, yet slow waves occurring under anesthesia present no positive effects on memory. Here, we shed light onto this paradox, based on a combination of extracellular recordings in vivo, in vitro, and computational models. We find two types of slow waves, based on analyzing the temporal patterns of successive slow-wave events. The first type is consistently observed in natural slow-wave sleep, while the second is shown to be ubiquitous under anesthesia. Network models of spiking neurons predict that the two slow wave types emerge due to a different gain on inhibitory vs excitatory cells and that different levels of spike-frequency adaptation in excitatory cells can account for dynamical distinctions between the two types. This prediction was tested in vitro by varying adaptation strength using an agonist of acetylcholine receptors, which demonstrated a neuromodulatory switch between the two types of slow waves. Finally, we show that the first type of slow-wave dynamics is more sensitive to external stimuli, which can explain how slow waves in sleep and anesthesia differentially affect memory consolidation, as well as provide a link between slow-wave dynamics and memory diseases.

neuroscience↗

bioRxiv2017

Inverse correlation processing by neurons with active dendrites

Many neurons possess dendrites enriched with sodium channels and are capable of generating action potentials. However, the role of dendritic sodium spikes remain unclear. Here, we study computational models of neurons to investigate the functional effects of dendritic spikes. In agreement with previous studies, we found that point neurons or neurons with passive dendrites increase their somatic firing rate in response to the correlation of synaptic bombardment for a wide range of input conditions, i.e. input firing rates, synaptic conductances or refractory periods. However, neurons with active dendrites show the opposite behavior: for a wide range of conditions the firing rate decreases as a function of correlation. We found this property in three types of models of dendritic excitability: a Hodgkin-Huxley model of dendritic spikes, a model with integrate-and-fire dendrites, and a discrete-state dendritic model. We conclude that neurons equipped with with fast dendritic spikes confer much broader computational properties to neurons, sometimes opposite to that of point neurons.

neuroscience↗