Cortical Network Synchrony Under Applied Electrical Field

Synchronous network activity plays a crucial role in complex brain functions. Stimulating the nervous system with applied electric field (EF) is a common tool for probing network responses. We used a gold wire-embedded silk protein film-based interface culture to investigate the effects of applied EFs on random cortical networks of in vitro cultures. Two-week-old cultures were exposed to EF of 27 mV/mm for \u3c1 h and monitored by time-lapse calcium imaging. Network activity was represented by calcium signal time series mapped to source neurons and analyzed by using a community detection algorithm. Cortical cultures exhibited large scale, synchronized oscillations under alternating EF of changing frequencies. Field polarity and frequency change were both found to be necessary for network synchrony, as monophasic pulses of similar frequency changes or EF of a constant frequency failed to induce correlated activities of neurons. Group-specific oscillatory patterns were entrained by network-level synchronous oscillations when the alternating EF frequency was increased from 0.2 Hz to 200 kHz. Binary responses of either activity increase or decrease contributed to the opposite phase patterns of different sub-populations. Conversely, when the EF frequency decreased over the same range span, more complex behavior emerged showing group-specific amplitude and phase patterns. These findings formed the basis of a hypothesized network control mechanism for temporal coordination of distributed neuronal activity, involving coordinated stimulation by alternating polarity, and time delay by change of frequency. These novel EF effects on random neural networks have important implications for brain functional studies and neuromodulation applications

Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature.

Despite in vivo malignancy, ependymoma lacks cell culture models, thus limiting therapy development. Here, we used a tunable three-dimensional (3D) culture system to approximate the ependymoma microenvironment for recapitulating a patient\u27s tumor in vitro. Our data showed that the inclusion of VEGF in serum-free, mixed neural and endothelial cell culture media supported the in vitro growth of all four ependymoma patient samples. The growth was driven by Nestin and Ki67 double-positive cells in a putative cancer stem cell niche, which was manifested as rosette-looking clusters in 2D and spheroids in 3D. The effects of extracellular matrix (ECM) such as collagen or Matrigel superseded that of the media conditions, with Matrigel resulting in the greater enrichment of Nestin-positive cells. When mixed with endothelial cells, the 3D co-culture models developed capillary networks resembling the in vivo ependymoma vasculature. The transcriptomic analysis of two patient cases demonstrated the separation of in vitro cultures by individual patients, with one patient\u27s culture samples closely clustered with the primary tumor tissue. While VEGF was found to be necessary for preserving the transcriptomic features of in vitro cultures, the presence of endothelial cells shifted the gene\u27s expression patterns, especially genes associated with ECM remodeling. The homeobox genes were mostly affected in the 3D in vitro models compared to the primary tumor tissue and between different 3D formats. These findings provide a basis for understanding the ependymoma microenvironment and enabling the further development of patient-derived in vitro ependymoma models for personalized medicine

Cortical Network Synchrony Under Applied Electrical Field in vitro

Synchronous network activity plays a crucial role in complex brain functions. Stimulating the nervous system with applied electric field (EF) is a common tool for probing network responses. We used a gold wire-embedded silk protein film-based interface culture to investigate the effects of applied EFs on random cortical networks of in vitro cultures. Two-week-old cultures were exposed to EF of 27 mV/mm for <1 h and monitored by time-lapse calcium imaging. Network activity was represented by calcium signal time series mapped to source neurons and analyzed by using a community detection algorithm. Cortical cultures exhibited large scale, synchronized oscillations under alternating EF of changing frequencies. Field polarity and frequency change were both found to be necessary for network synchrony, as monophasic pulses of similar frequency changes or EF of a constant frequency failed to induce correlated activities of neurons. Group-specific oscillatory patterns were entrained by network-level synchronous oscillations when the alternating EF frequency was increased from 0.2 Hz to 200 kHz. Binary responses of either activity increase or decrease contributed to the opposite phase patterns of different sub-populations. Conversely, when the EF frequency decreased over the same range span, more complex behavior emerged showing group-specific amplitude and phase patterns. These findings formed the basis of a hypothesized network control mechanism for temporal coordination of distributed neuronal activity, involving coordinated stimulation by alternating polarity, and time delay by change of frequency. These novel EF effects on random neural networks have important implications for brain functional studies and neuromodulation applications

Cortical Network Synchrony Under Applied Electrical Field in vitro

Synchronous network activity plays a crucial role in complex brain functions. Stimulating the nervous system with applied electric field (EF) is a common tool for probing network responses. We used a gold wire-embedded silk protein film-based interface culture to investigate the effects of applied EFs on random cortical networks of in vitro cultures. Two-week-old cultures were exposed to EF of 27 mV/mm for \u3c1 h and monitored by time-lapse calcium imaging. Network activity was represented by calcium signal time series mapped to source neurons and analyzed by using a community detection algorithm. Cortical cultures exhibited large scale, synchronized oscillations under alternating EF of changing frequencies. Field polarity and frequency change were both found to be necessary for network synchrony, as monophasic pulses of similar frequency changes or EF of a constant frequency failed to induce correlated activities of neurons. Group-specific oscillatory patterns were entrained by network-level synchronous oscillations when the alternating EF frequency was increased from 0.2 Hz to 200 kHz. Binary responses of either activity increase or decrease contributed to the opposite phase patterns of different sub-populations. Conversely, when the EF frequency decreased over the same range span, more complex behavior emerged showing group-specific amplitude and phase patterns. These findings formed the basis of a hypothesized network control mechanism for temporal coordination of distributed neuronal activity, involving coordinated stimulation by alternating polarity, and time delay by change of frequency. These novel EF effects on random neural networks have important implications for brain functional studies and neuromodulation applications

Biotech start-ups in the US and Germany.

This project is concerned with biotechnology start-up companies in the United States and Germany. The focus is a comparison of variables surrounding biotechnology start-up companies in both countries. Using interviews and a case study, the roles of these variables were analyzed. Through research, it has become apparent that despite needing further improvement in Germany, these variables have created a favorable environment for biotech start-up companies. A manual of recommendations was also created to aid entrepreneurs in starting biotechnology companies