Frontiers in Cellular Neuroscience

Journal: Frontiers in Cellular Neuroscience

Abbreviation

Front Cell Neurosci

Publisher

Frontiers Media

ISSN

1662-5102

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Publications 1 - 10 of 17

Editorial: Methods and applications in cellular neurophysiology
Delvendahl, Igor; Hu, Bo; Murphy, Jonathan G. (2023)
Frontiers in Cellular Neuroscience
The Predictive Value of Individual Electric Field Modeling for Transcranial Alternating Current Stimulation Induced Brain Modulation
Preisig, Basil C.; Hervais-Adelman, Alexis (2022)
Frontiers in Cellular Neuroscience
There is considerable individual variability in the reported effectiveness of non-invasive brain stimulation. This variability has often been ascribed to differences in the neuroanatomy and resulting differences in the induced electric field inside the brain. In this study, we addressed the question whether individual differences in the induced electric field can predict the neurophysiological and behavioral consequences of gamma band tACS. In a within-subject experiment, bi-hemispheric gamma band tACS and sham stimulation was applied in alternating blocks to the participants' superior temporal lobe, while task-evoked auditory brain activity was measured with concurrent functional magnetic resonance imaging (fMRI) and a dichotic listening task. Gamma tACS was applied with different interhemispheric phase lags. In a recent study, we could show that anti-phase tACS (180 degrees interhemispheric phase lag), but not in-phase tACS (0 degrees interhemispheric phase lag), selectively modulates interhemispheric brain connectivity. Using a T1 structural image of each participant's brain, an individual simulation of the induced electric field was computed. From these simulations, we derived two predictor variables: maximal strength (average of the 10,000 voxels with largest electric field values) and precision of the electric field (spatial correlation between the electric field and the task evoked brain activity during sham stimulation). We found considerable variability in the individual strength and precision of the electric fields. Importantly, the strength of the electric field over the right hemisphere predicted individual differences of tACS induced brain connectivity changes. Moreover, we found in both hemispheres a statistical trend for the effect of electric field strength on tACS induced BOLD signal changes. In contrast, the precision of the electric field did not predict any neurophysiological measure. Further, neither strength, nor precision predicted interhemispheric integration. In conclusion, we found evidence for the dose-response relationship between individual differences in electric fields and tACS induced activity and connectivity changes in concurrent fMRI. However, the fact that this relationship was stronger in the right hemisphere suggests that the relationship between the electric field parameters, neurophysiology, and behavior may be more complex for bi-hemispheric tACS.
microRNA-dependent regulation of gene expression in GABAergic interneurons
Kołosowska, Karolina Anna; Schratt, Gerhard; Winterer, Jochen (2023)
Frontiers in Cellular Neuroscience
Information processing within neuronal circuits relies on their proper development and a balanced interplay between principal and local inhibitory interneurons within those circuits. Gamma-aminobutyric acid (GABA)ergic inhibitory interneurons are a remarkably heterogeneous population, comprising subclasses based on their morphological, electrophysiological, and molecular features, with differential connectivity and activity patterns. microRNA (miRNA)-dependent post-transcriptional control of gene expression represents an important regulatory mechanism for neuronal development and plasticity. miRNAs are a large group of small non-coding RNAs (21-24 nucleotides) acting as negative regulators of mRNA translation and stability. However, while miRNA-dependent gene regulation in principal neurons has been described heretofore in several studies, an understanding of the role of miRNAs in inhibitory interneurons is only beginning to emerge. Recent research demonstrated that miRNAs are differentially expressed in interneuron subclasses, are vitally important for migration, maturation, and survival of interneurons during embryonic development and are crucial for cognitive function and memory formation. In this review, we discuss recent progress in understanding miRNA-dependent regulation of gene expression in interneuron development and function. We aim to shed light onto mechanisms by which miRNAs in GABAergic interneurons contribute to sculpting neuronal circuits, and how their dysregulation may underlie the emergence of numerous neurodevelopmental and neuropsychiatric disorders.
Heritable and inducible gene knockdown in astrocytes or neurons in vivo by a combined lentiviral and RNAi approach
Heitz, Fabrice; Johansson, Tornjörn; Baumgärtel, Karsten; et al. (2014)
Frontiers in Cellular Neuroscience
Gene knockout by homologous recombination is a popular method to study gene functions in the mouse in vivo. However, its lack of temporal control has limited the interpretation of knockout studies because the complete elimination of a gene product often alters developmental processes, and can induce severe malformations or lethality. Conditional gene knockdown has emerged as a compelling alternative to gene knockout, an approach well-established in vitro but that remains challenging in vivo, especially in the adult brain. Here, we report a method for conditional and cell-specific gene knockdown in the mouse brain in vivo that combines Cre-mediated RNA interference (RNAi) with classical and lentivirus-mediated transgenesis. The method is based on the inducible expression of a silencing short hairpin RNA (shRNA) introduced in mice by lentivirus-mediated transgenesis, and on its activation by excision of a floxed stop EGFP reporter with an inducible Cre recombinase expressed in astrocytes or in neurons. This dual system should be of broad utility for comparative studies of gene functions in these two cell types in vivo.
Shedding of APP limits its synaptogenic activity and cell adhesion properties
Stahl, Ronny; Schilling, Sandra; Soba, Peter; et al. (2014)
Frontiers in Cellular Neuroscience
The amyloid precursor protein (APP) plays a central role in Alzheimer’s disease (AD) and has essential synapse promoting functions. Synaptogenic activity as well as cell adhesion properties of APP presumably depend on trans-cellular dimerization via its extracellular domain. Since neuronal APP is extensively processed by secretases, it raises the question if APP shedding affects its cell adhesion and synaptogenic properties. We show that inhibition of APP shedding using cleavage deficient forms of APP or a dominant negative α-secretase strongly enhanced its cell adhesion and synaptogenic activity suggesting that synapse promoting function of APP is tightly regulated by α-secretase mediated processing, similar to other trans-cellular synaptic adhesion molecules.
Dual-mode Microelectrode Array with 20k-electrodes and High SNR for High-Throughput Extracellular Recording and Stimulation
Yuan, Xinyue; Hierlemann, Andreas; Frey, Urs (2018)
Frontiers in Cellular Neuroscience ~ Conference Abstract: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays
Improved Generation of Induced Pluripotent Stem Cells From Hair Derived Keratinocytes - A Tool to Study Neurodevelopmental Disorders as ADHD
Re, Silvano; Dogan, Asli A.; Ben-Shachar, Dorit; et al. (2018)
Frontiers in Cellular Neuroscience
In the last decade, there is an increasing application of induced pluripotent stem cells (iPSCs) for disease modeling. The iPSC technology enables the study of patient-specific neuronal cell lines in vitro to evaluate dysfunction at the cellular level and identify the responsible genetic factors. This approach might be particularly valuable for filling the gap of knowledge at the cellular and molecular levels underlying the pathophysiology of various neurodevelopmental and/or psychiatric disorders, such as attention-deficit hyperactivity disorder (ADHD). However, the invasiveness of skin biopsy or blood withdrawal might represent a major impediment in such protected population. Using hair derived keratinocytes as starting somatic cells circumvents this problem as sample collections can be performed non-invasively. Here we describe an improved, convenient, standardized and effective method to culture and reprogram hair derived keratinocytes from three healthy controls and one ADHD patient into iPSCs, which in turn will be used to generate differentiated neuronal cells. All the cell types were maintained in highly defined, serum-free conditions and showed expression of the respective key marker genes, assessed by both immunocytochemistry and qRT-PCR. The described in vitro personalized neuronal model has its advantage in modeling neurodevelopmental trajectories since it can recapitulate key processes of brain development at the cellular and molecular level and is intended to be used as for example studying ADHD etiopathology.
Development and Application of Sub-Mitochondrial Targeted Ca2 + Biosensors
Waldeck-Weiermair, Markus; Gottschalk, Benjamin; Madreiter-Sokolowski, Corina T.; et al. (2019)
Frontiers in Cellular Neuroscience
Mitochondrial Ca2+ uptake into the mitochondrial matrix is a well-established mechanism. However, the sub-organellar Ca2+ kinetics remain elusive. In the present work we identified novel site-specific targeting sequences for the intermembrane space (IMS) and the cristae lumen (CL). We used these novel targeting peptides to develop green- and red- Ca2+ biosensors targeted to the IMS and to the CL. Based on their distinctive spectral properties, and comparable sensitivities these novel constructs were suitable to visualize Ca2+-levels in various (sub) compartments in a multi-chromatic manner. Functional studies that applied these new biosensors revealed that knockdown of MCU and EMRE yielded elevated Ca2+ levels inside the CL but not the IMS in response to IP3-generating agonists. Knockdown of VDAC1, however, strongly impeded the transfer of Ca2+ through the OMM while the cytosolic Ca2+ signal remained unchanged. The novel sub-mitochondrially targeted Ca2+ biosensors proved to be suitable for Ca2+ imaging with high spatial and temporal resolution in a multi-chromatic manner allowing simultaneous measurements. These informative biosensors will facilitate efforts to dissect the complex sub-mitochondrial Ca2+ signaling under (patho)physiological conditions.
Technologies to Study Action Potential Propagation With a Focus on HD-MEAs
Emmenegger, Vishalini; Obien, Marie Engelene J.; Franke, Felix; et al. (2019)
Frontiers in Cellular Neuroscience
Axons convey information in neuronal circuits via reliable conduction of action potentials (APs) from the axon initial segment (AIS) to the presynaptic terminals. Recent experimental findings increasingly evidence that the axonal function is not limited to the simple transmission of APs. Advances in subcellular-resolution recording techniques have shown that axons display activity-dependent modulation in spike shape and conduction velocity, which influence synaptic strength and latency. We briefly review here, how recent methodological developments facilitate the understanding of the axon physiology. We included the three most common methods, i.e., genetically encoded voltage imaging (GEVI), subcellular patch-clamp and high-density microelectrode arrays (HD-MEAs). We then describe the potential of using HD-MEAs in studying axonal physiology in more detail. Due to their robustness, amenability to highthroughput and high spatiotemporal resolution, HD-MEAs can provide a direct functional electrical readout of single cells and cellular ensembles at subcellular resolution. HDMEAs can, therefore, be employed in investigating axonal pathologies, the effects of large-scale genomic interventions (e.g., with RNAi or CRISPR) or in compound screenings. A combination of extracellular microelectrode arrays (MEAs), intracellular microelectrodes and optical imaging may potentially reveal yet unexplored repertoires of axonal functions.
Electrophysiological phenotype characterization of human iPSC-derived dopaminergic neuronal lines by means of high-resolution microelelectrode arrays
Fiscella, Michele; Leary, Noelle; Acun, Ebru; et al. (2018)
Frontiers in Cellular Neuroscience ~ Conference Abstract: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays

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