Biology subjects

Vandenberghe, M.

Publications and source records attributed to Vandenberghe, M..

3 recordsLinked to original sources

bioRxiv2021

All-optical electrophysiology in hiPSC-derived neurons with synthetic voltage sensors

Voltage imaging and "all-optical electrophysiology" in human induced pluripotent stem cell (hiPSC)-derived neurons have opened unprecedented opportunities for high-throughput phenotyping of activity in neurons possessing unique genetic backgrounds of individual patients. While prior all-optical electrophysiology studies relied on genetically encoded voltage indicators, viral transduction of human neurons with large or multiple expression vectors can impact cell function and often lead to massive cell death. Here, we demonstrate an alternative protocol using a synthetic voltage sensor and genetically encoded optogenetic actuator that generate robust and reproducible results. We demonstrate the functionality of this method by measuring spontaneous and evoked activity in three independent hiPSC-derived neuronal cell lines with distinct genetic backgrounds.

neuroscience↗

bioRxiv2020

A human iPSC-astroglia neurodevelopmental model reveals divergent transcriptomic patterns in schizophrenia

While neurodevelopmental abnormalities have been associated with schizophrenia (SCZ), the role of astroglia in disease pathophysiology remains poorly understood. In this study we used a human induced pluripotent stem cell (iPSC)-derived astrocyte model to investigate the temporal patterns of astroglia differentiation during developmental stages critical for SCZ using RNA-sequencing. The model generated astrocyte-specific patterns of gene expression during differentiation, and demonstrated that these patterns correspond well to astroglia-specific expression signatures of in vivo cortical fetal development. Applying this model, we were able to identify SCZ-specific expression dynamics in human astrocytes, and found that SCZ-associated differentially expressed genes were significantly enriched in the medial prefrontal cortex, striatum, and temporal lobe, targeting VWA5A and ADAMTS19. In addition, SCZ astrocytes displayed alterations in calcium signaling, and significantly decreased glutamate uptake and metalloproteinase activity relative to controls. These results provide strong support for the validity of our astrocyte model, and implicate novel transcriptional dynamics in astrocyte differentiation in SCZ together with functional changes that are potentially important biological components of SCZ pathology.

neuroscience↗

bioRxiv2018

Nested oscillatory dynamics in cortical organoids model early human brain network development

Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed cortical organoids that spontaneously display periodic and regular oscillatory network events that are dependent on glutamatergic and GABAergic signaling. These nested oscillations exhibit cross-frequency coupling, proposed to coordinate neuronal computation and communication. As evidence of potential network maturation, oscillatory activity subsequently transitioned to more spatiotemporally irregular patterns, capturing features observed in preterm human electroencephalography (EEG). These results show that the development of structured network activity in the human neocortex may follow stable genetic programming, even in the absence of external or subcortical inputs. Our approach provides novel opportunities for investigating and manipulating the role of network activity in the developing human cortex.\n\nHIGHLIGHTSO_LIEarly development of human functional neural networks and oscillatory activity can be modeled in vitro.\nC_LIO_LICortical organoids exhibit phase-amplitude coupling between delta oscillation (2 Hz) and high-frequency activity (100-400 Hz) during network-synchronous events.\nC_LIO_LIDifferential role of glutamate and GABA in initiating and maintaining oscillatory network activity.\nC_LIO_LIDevelopmental impairment of MECP2-KO cortical organoids impacts the emergence of oscillatory activity.\nC_LIO_LICortical organoid network electrophysiological signatures correlate with human preterm neonatal EEG features.\nC_LI\n\neTOCBrain oscillations are a candidate mechanism for how neural populations are temporally organized to instantiate cognition and behavior. Cortical organoids initially exhibit periodic and highly regular nested oscillatory network events that eventually transition to more spatiotemporally complex activity, capturing features of late-stage preterm infant electroencephalography. Functional neural circuitry in cortical organoids exhibits emergence and development of oscillatory network dynamics similar to those found in the developing human brain.

neuroscience↗