Enhancement of Cortical Network Activity in vitro and Promotion of GABAergic Neurogenesis by Stimulation with an Electromagnetic Field with a 150 MHz Carrier Wave Pulsed with an Alternating 10 and 16 Hz Modulation

Abstract

In recent years, various stimuli were identified capable of enhancing neurogenesis, a process which is dysfunctional in the senescent brain and in neurodegenerative and certain neuropsychiatric diseases. Applications of electromagnetic fields to brain tissue have been shown to affect cellular properties and their importance for therapies in medicine is recognized. In this study, differentiating murine cortical networks on multiwell microelectrode arrays were repeatedly exposed to an extremely low-electromagnetic field (ELEMF) with alternating 10 and 16 Hz frequencies piggy backed onto a 150 MHz carrier frequency. The ELEMF exposure stimulated the electrical network activity and intensified the structure of bursts. Further, the exposure to electromagnetic fields within the first 28 days in vitro of the differentiation of the network activity induced also reorganization within the burst structure. This effect was already most pronounced at 14 days in vitro after 10 days of exposure. Overall, the development of cortical activity under these conditions was accelerated. These functional electrophysiological changes were accompanied by morphological ones. The percentage of neurons in the neuron glia co-culture was increased without affecting the total number of cells, indicating an enhancement of neurogenesis. The ELEMF exposure selectively promoted the proliferation of a particular population of neurons, evidenced by the increased proportion of GABAergic neurons. The results support the initial hypothesis that this kind of ELEMF stimulation could be a treatment option for specific indications with promising potential for CNS applications, especially for degenerative diseases, such as Alzheimer’s disease and other dementias.

Functional characterization of GABAA receptor-mediated modulation of cortical neuron network activity in microelectrode array recordings

“…This neuron/glia ratio of ~0.25 differs from the reported neuron/glia ratio of ~0.8 in mouse frontal cortex in vivo [ 33 ]. On the other hand, we have previously determined that approximately 20% of the neurons in these cultures are GABAergic neurons, which is in excellent agreement with ratio of GABAergic neurons (relative to total number of neurons) in mouse frontal cortex in vivo [ 30 , 34 ]. In the present study, we investigated the composition of the cortical networks and the nature and degree of synapse formation in them by means of immunocytochemistry using antibodies targeting synapsin-1, β3-tubulin and Hoechst-Bisbenzimid as markers for synaptic punctae, neurons and nuclei, respectively (n = 6).…”

“…As mentioned in section 2.2, the primary neurons were used for the MEA recordings between 28 and 35 days in vitro . Due to the serum used in the culture medium glia survival is supported in these cultures, and mainly because of proliferation of glia during the first 4 days after plating these neuron-glia co-cultures thus consist of approximately 20% neurons and 80% astrocytes including 1% microglia [ 30 ]. This neuron/glia ratio of ~0.25 differs from the reported neuron/glia ratio of ~0.8 in mouse frontal cortex in vivo [ 33 ].…”

“…In the figures in this study, heat map presentations depicting the changes induced by the various pharmacological tools in 40 of the 204 activity parameters are given together with concentration-response curves for 10 selected activity parameters. The definitions of some of these activity parameters have been presented in a recent publication [ 30 ], and the definitions of all 40 parameters shown in the figures are given in S1 Table . In brief: spike rate : number of spikes per second, averaged over all spike trains recorded per 60 s bin; burst rate : number of bursts per second, a measure for burstiness of units averaged over all units recorded per 60 s bin; burst duration : mean lengths of bursts (in ms) based on inter-spike interval (ISI) method; burst amplitude : bursts are mathematically superimposed with an integral function defined by spike peak density in bursts and number of spikes, and burst amplitude is the peak amplitude of the integrated burst reflecting the fraction of the bursts with highest spike density; spike rate SD and burst rate SD : SD of spike and burst rate, respectively, across 60 s bins, indicating the variability of spikiness and burstiness of units within temporal episodes; spike rate CVnet and burst rate CVnet : coefficient of variation of spike and burst rate, respectively, reflecting spatial variation of spike and burst rate over the network during experimental episodes; Syn All : average distance of bursts within a population burst from population burst center, a measure for the strength of synchronicity of a network; Spike Simplex; spike trains are divided into timeframes of 1 ms bin-size, and within these bins different units within the network generate spikes.…”

The effects of transcranial alternating current stimulation (tACS) at individual alpha peak frequency (iAPF) on motor cortex excitability in young and elderly adults

“…Driving gamma oscillations using tACS modulates inhibition in the human motor cortex (Nowak et al 2017 ). Similarly, studies with rodents have shown that exposure to an extremely low-electromagnetic field (ELEMF) with alternating 10 and 16 Hz frequencies increased and intensified the burst structure in rodent’s cortical in vitro networks, as well as increasing the population of GABAergic neurons (Gramowski-Voss et al 2015 ). We also suggest that the net increase in inhibition in the motor cortex of the old group due to the stimulation was responsible for the lower facilitation of MEP amplitudes in the single-pulse TMS paradigm, the MEP recruitment in the I / O curve and possibly the ICF, which remained unchanged after stimulation in the old group.…”

Nanovoltmetric / Nanoammetric Analyzer for Carrier Wave Modulation Measurements in Quantitative Bioacoustics

“…К сожалению, в нейронауки и биоакустику данные разработки в тот период практически не поступают. Редкие исключения (например, работы по усилению волновой активности кортикальных нейросетей и их морфогенеза in vitro при стимуляции отдельными частотами (например, 150 МГц несущей при подаче пакетов сигналов с частотой 10-16 Гц) [97] только подтверждают правило, так как нейроэлектрофизиологические частоты не лежат в этом диапазоне несущей, а воздействие явно имеет физико-химический характер, а не модулирует активность нейросетей.…”