Cortical Network Synchrony Under Applied Electrical Field in vitro

Abstract

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.

Ultra‐Sharp Nanowire Arrays Natively Permeate, Record, and Stimulate Intracellular Activity in Neuronal and Cardiac Networks

“…The synchronized neuronal activity is a common phenomenon in neuronal cultures with multielectrode arrays [ 41 ] and is related to the stage of neuron development and the neuron–glia interactions, [ 41,42 ] and plays a crucial role in complex brain function and neurological diseases. [ 43–45 ] The observed spike synchronicity likely originated from our multilayered, largely neuronal cultures (Figure S12, Supporting Information) with reduced isolation between neurons by glia and without the in vivo molecular heterogeneity composed of extracellular matrices that usually result in heterogeneity in firing in the brain. Thus, 13 and 15 DIV traces show two or multiple continuous spikes.…”

“…The synchronized neuronal activity is a common phenomenon in neuronal cultures with multi-electrode arrays [25] and is related to the stage of neuron development and the neuron-glia interactions, [25,26] and plays a crucial role in complex brain functions and neurological disorders. [27][28][29] The observed spike synchronicity likely originated from our multilayered, strictly neuronal cultures with no isolation between neurons by glia and without the in vivo molecular heterogeneity composed of extracellular matrices that usually result in heterogeneity in firing in the brain. Clear variance in spike counts across 32 channels in Figure 2g at 19 DIV and the evident variations in graded subthreshold potentials before action potential spikes in Figure 2i confirm non-shorted, strong intracellular USNW-neuron interfaces across the recorded channels.…”

Functional maturation of human neural stem cells in a 3D bioengineered brain model enriched with fetal brain-derived matrix

“…For each time point (i.e., 3 and 7 months) and type of construct (i.e., fetal ECM, adult ECM, or Collagen I), the ROIs isolated in n = 3 cultures were collected and a feature-based cluster analysis of the Δ F / F signals from these ROIs was conducted as in Tang-Schomer et al . 88 . Briefly, each Δ F / F was processed to compute a feature vector consisting of 8 distinct features (see definition in Supplemental Methods ), which collectively provide a time-frequency characterization that is unique to the Δ F / F signal.…”

Functional maturation of human neural stem cells in a 3D bioengineered brain model enriched with fetal brain-derived matrix

“…The Δ F / F signals collected from the isolated ROIs were used for cluster analysis as in (Tang-Schomer, Jackvony, & Santaniello, 2018). Briefly, each Δ F / F was processed to compute the following features, which collectively provide a time-frequency characterization that is unique to the Δ F / F signal: where Δ F / F ( k ) is the k -th sample in the Δ F / F time series, N is the total number of samples in Δ F / F , μ is the average value of Δ F/F , and P Δ F / F ( ω ) is the power spectrum density of the Δ F / F signal at frequency 0≤ ω ≤ F s /2, where F s is the number of frames per second.…”