Biology subjects

Frey, U.

Publications and source records attributed to Frey, U..

4 recordsLinked to original sources

bioRxiv2020

Versatile live-cell activity analysis platform for characterization of neuronal dynamics at single-cell and network level

Chronic imaging of neuronal networks in vitro has provided fundamental insights into mechanisms underlying neuronal function. Existing labeling and optical imaging methods, however, cannot be used for continuous and long-term recordings of the dynamics and evolution of neuronal networks, as fluorescence indicators can cause phototoxicity. Here, we introduce a versatile platform for label-free, comprehensive and detailed electrophysiological live-cell imaging of various neurogenic cells and tissues over extended times. We report on a novel dual-mode high-density microelectrode array, which can simultaneously record in i) full-frame mode with 19,584 recording sites and ii) high-signal-to-noise mode with 246 channels. We set out to demonstrate the capabilities of this platform with recordings from primary and iPSC-derived neuronal cultures and tissue preparations over several weeks, providing detailed morpho-electrical phenotypic parameters at subcellular, cellular and network level. Moreover, we developed reliable analysis tools with drastically increased throughput for extracting axonal morphology and conduction parameters.

neuroscience↗

bioRxiv2019

Loss of adaptive capacity in asthmatics revealed by biomarker fluctuation dynamics on experimental rhinovirus challenge

Asthma is a dynamic disease, in which lung mechanical and inflammatory processes often interact in a complex, unpredictable manner. We hypothesize that this may be explained by respiratory disease-related systems instability and loss of adaptability to changing environmental conditions, resulting in highly fluctuating biomarkers and symptoms. Using time series of inflammatory (eosinophils, neutrophils, FeNO), clinical and lung function biomarkers (PEF, FVC, and FEV1), we estimated this loss of adaptive capacity (AC) during an experimental perturbation with a rhinovirus in 24 healthy and asthmatic volunteers. Loss of AC was estimated by comparing similarities between pre- and post-challenge time series. Unlike healthy participants, the asthmatics post-viral-challenge state resembled significantly more other rhinovirus-infected asthmatics than their own pre-viral-challenge state (hypergeometric-test: p=0.029). This reveals loss of AC, and supports the novel concept that not only single physiological mechanisms, but interacting dynamic disease properties are altered in asthma and contribute to a more vulnerable phenotype.

physiology↗

bioRxiv2018

The axon initial segment drives the neuron’s extracellular action potential

Extracellular voltage fields produced by a neurons action potentials provide a primary means for studying neuron function, yet their biophysical sources remain ambiguous. The neurons soma and dendrites are thought to drive the extracellular action potential (EAP), while the axon is usually ignored. However, by recording voltages of single neurons in dissociated rat cortical cultures and Purkinje cells in acute mouse cerebellar slices at hundreds of sites, we find instead that the axon initial segment dominates the EAP, and, surprisingly, the soma shows little or no influence. As expected, this signal has negative polarity (charge entering the cell) and initiates at the distal end. Interestingly, signals with positive polarity (charge exiting the cell) occur near some but not all dendritic branches and occur after a delay. Such basic knowledge about which neuronal compartments contribute to the extracellular voltage field is important for interpreting results from all electrical readout schemes. Moreover, this finding shows that changes in the AIS position and function can be observed in high spatiotemporal detail by means of high-density extracellular electrophysiology.\n\nKey points summaryO_LIThe neurons soma and dendrites are thought to give rise to its extracellular voltage signal, while signals from the axon are usually considered negligible.\nC_LIO_LIInstead, we found that the largest amplitude of the extracellular signal originates from the axon initial segment, not from the soma.\nC_LIO_LIThis finding shows that changes in the AIS position and function can be observed in high spatiotemporal detail by means of high-density extracellular electrophysiology.\nC_LI\n\nAbbreviations

neuroscience↗

bioRxiv2017

Network Analysis Of High-Density Microelectrode Recordings

A high-density microelectrode arrays (HDMEA) with 3,150 electrodes per square millimetre was used to capture neuronal activity across various scales, including axons, dendrites, and networks. We present a new method for high-throughput segmentation of axons based on the spatial smoothness of signal delays. Comparison with both ground truth and receiver operator characteristics shows that the new segmentation method outperforms previous methods based on the signal-amplitude-to-noise ratio. Structural and functional neuronal network connectivity were reconstructed using a common extension of \"Peters rule\" and a inter-spike histogram method, respectively. Approximately one third of these connections are putative chemical synapses. We evaluated the spike patterns but did not find evidence for \"polychronisation\" (non-synchronous but precisely timed spike sequences). The developed framework can be used to investigate the relationship between the topology of neuronal connections and emerging temporal spike patterns observed in dissociated neuronal cultures.

neuroscience↗