So far, the only identified biological effects of radiofrequency fields (RF) are known to be caused by heating but the issue of potential nonthermal biological effects, especially on the central nervous system (CNS), remains open. We previously reported a decrease in the firing and bursting rates of neuronal cultures exposed to a Global System for Mobile (GSM) RF field at 1800 MHz for 3 min (Moretti et al. 2013). The aim of the present work was to assess the dose-response relationship for this effect, and also identify a potential differential response elicited by pulse-modulated GSM and continuous-wave (CW) RF fields. Spontaneous bursting activity of neuronal cultures from rat embryonic cortices was recorded using 60-electrode Multi Electrode Arrays (MEAs). At 17-28 days in vitro, the neuronal cultures were subjected to 15-min RF exposures, at SARs (Specific Absorption Rates) ranging from 0.01 to 9.2 W/kg. Both GSM and CW signals elicited a clear decrease in bursting rate during the RF exposure phase. This effect became more marked with increasing SAR and lasted even beyond the end of exposure for the highest SAR levels. Moreover, the amplitude of the effect was greater with the GSM signal. Altogether, our experimental findings provide evidence for dose-dependent effects of RF signals on the bursting rate of neuronal cultures and suggest that part of the mechanism is nonthermal.

The central nervous system is the most likely target of mobile telephony radiofrequency (RF) field exposure in terms of biological effects. Several electroencephalography (EEG) studies have reported variations in the alpha-band power spectrum during and/or after RF exposure, in resting EEG and during sleep. In this context, the observation of the spontaneous electrical activity of neuronal networks under RF exposure can be an efficient tool to detect the occurrence of low-level RF effects on the nervous system. Our research group has developed a dedicated experimental setup in the GHz range for the simultaneous exposure of neuronal networks and monitoring of electrical activity. A transverse electromagnetic (TEM) cell was used to expose the neuronal networks to GSM-1800 signals at a SAR level of 3.2 W/kg. Recording of the neuronal electrical activity and detection of the extracellular spikes and bursts under exposure were performed using microelectrode arrays (MEAs). This work provides the proof of feasibility and preliminary results of the integrated investigation regarding exposure setup, culture of the neuronal network, recording of the electrical activity, and analysis of the signals obtained under RF exposure. In this pilot study on 16 cultures, there was a 30% reversible decrease in firing rate (FR) and bursting rate (BR) during a 3 min exposure to RF. Additional experiments are needed to further characterize this effect.

Local control of protein translation is a fundamental process for the regulation of synaptic plasticity. It has been demonstrated that the local protein synthesis occurring in axons and dendrites can be shaped by numerous mechanisms, including miRNA-mediated regulation. However, several aspects underlying this regulatory process have not been elucidated yet.Here we analyze the differential miRNA profile in cell bodies and neurites of primary hippocampal neurons and find an enrichment of the precursor and mature forms of miR-218 in the neuritic projections. We show that miR-218 abundance is regulated during hippocampal development and by chronic silencing or activation of neuronal network. Overexpression and knockdown of miR-218 demonstrated that miR-218 targets the mRNA encoding the GluA2 subunit of AMPA receptors and modulates its expression. At the functional level, miR-218 overexpression increases glutamatergic synaptic transmission at both single neuron and network levels. Our data demonstrate a key role for miR-218 in the regulation of AMPAmediated excitatory transmission and in the homeostatic regulation of synaptic plasticity.

Magnetoencephalography has been established nowadays as a crucial in vivo technique for clinical and diagnostic applications due to its unprecedented spatial and temporal resolution and its non-invasive methods. However, the innate nature of the biomagnetic signals derived from active biological tissue is still largely unknown. One alternative possibility for in vitro analysis is the use of magnetic sensor arrays based on Magnetoresistance. However, these sensors have never been used to perform long-term in vitro studies mainly due to critical biocompatibility issues with neurons in culture. In this study, we present the first biomagnetic chip based on magnetic tunnel junction (MTJ) technology for cell culture studies and show the biocompatibility of these sensors. We obtained a full biocompatibility of the system through the planarization of the sensors and the use of a three-layer capping of SiO2/Si3N4/SiO2. We grew primary neurons up to 20 days on the top of our devices and obtained proper functionality and viability of the overlying neuronal networks. At the same time, MTJ sensors kept their performances unchanged for several weeks in contact with neurons and neuronal medium. These results pave the way to the development of high performing biomagnetic sensing technology for the electrophysiology of in vitro systems, in analogy with Multi Electrode Arrays.

The SystemC modules of the Link Manager Layer and Baseband Layer have been designed in this work at behavioral level to analyze the performances of the Bluetooth standard.In particular the probability of the creation of a piconet in presence of noise in the channel and the power reduction using the sniff and hold mode have been investigated. The Bluetooth StandardBluetooth is an emerging standard for short distance wireless communications developed by the Bluetooth Special Interest Group (SIG) [1].Bluetooth is a short-range (10-100m) wireless link technology aimed at replacing cables that connect phones, laptops, PDAs, and other portable devices.The Bluetooth standard operates at 2.4 GHz in the ISM band (Industrial Scientific Medicine) with GSFK modulation (Gaussian Frequency Shift Keying). The FHSS (Frequency Hopping Spread Spectrum) technique is used to reduce the effect of radio frequency interferences on transmission quality. The Bluetooth devices sharing the same channel form a network called piconet, with a single unit acting as a master, the other units acting as slaves. Up to eight devices constitute a piconet, with a master device coordinating access by a polling scheme.The channel is represented by a pseudo-random hopping sequence in the 79 RF channels of 1-MHz width. The raw data rate is 1 Mbit/s. The hopping sequence is unique for the piconet and is determined by the Bluetooth address of the master. The channel is divided into time slots, where each slot corresponds to an RF hop frequency. Consecutive hops correspond to different RF frequencies. The nominal hop rate is 1600 hops/s.A time division multiplexing (TDD) technique divides the channel into 625 µsecs slots and, with a 1-Mbit/s symbol rate, a slot can carry up to 625 bits.The standard defines two types of link between master and slaves: Synchronous Connection-Oriented (SCO) link, and Asynchronous Connection-Less (ACL) link.Many low cost Bluetooth devices are now available and many papers have been presented for the hardware implementation [2 and reference therein]. The Bluetooth protocol is complex and many research is in progress for choice of the parameters of the standard in order to optimize the efficiency of the standard itself.For example, Cordeiro [3] developed a model implementing the basic functionality of the Baseband, LMP and L2CAP layers to evaluate the impact of interference on the throughput. In [4,5] a theorical analysis of packet error rate of a Bluetooth piconet in proximity with other Bleutooth piconets and 802.11 WLANs is presented. Bluetooth Architecture in SystemCThe Bluetooth Stack, in Fig.1, goes from the high level Application layer to the low level radio frequency layer, the lower layers has been modeled in this work using the SystemC language. SystemC is an emerging standard modeling platform based on C++ that supports design abstraction at the RTL, behavioral and system level [6].Design methods for integrated circuits based on hardware description languages (such as VHDL or Verilog), when applied to these s...

Preliminary reports in patients with Parkinson's disease (PD) showed that subthalamic nucleus (STN) stimulation was able to reverse parkinsonian state. Since 1998 we evaluated the safety and the efficacy of STN stimulation in 7 patients affected by advanced PD. All patients were included using CAPIT protocol. Motor functions and quality of life were evaluated, before and after surgery, with UPDRS and PDQ38, respectively. At the 6-month follow-up, the off medication/on stimulation UPDRS motor score improved by 50.6% and the on medication/on stimulation by 20.3%. Motor fluctuations were reduced by 57.2% and dyskinesias by 73.5%. The total L-dopa equivalent daily dose was reduced by 40.7%. PDQ38 ameliorated by 49.9%. We did not observe any perioperatory complication and only mild and tolerable side effects after stimulation.

A promising strategy to get deeper insight on brain functionalities relies on the investigation of neural activities at the cellular and sub-cellular level. In this framework, methods for recording neuron electrical activity have gained interest over the years. Main technological challenges are associated to finding highly sensitive detection schemes, providing considerable spatial and temporal resolution. Moreover, the possibility to perform non-invasive assays would constitute a noteworthy benefit. In this work, we present a magnetoresistive platform for the detection of the action potential propagation in neural cells. Such platform allows, in perspective, the in vitro recording of neural signals arising from single neurons, neural networks and brain slices.

Magnetoencephalography (MEG) has revolutionized neuroscience, offering a tool with unprecedented spatial and temporal resolution. Today, MEG has clinical uses in detecting and localizing pathological activity in patients with brain tumors or intractable epilepsy [1].Despite the wide clinical applications, the nature of MEG signals at local level is still not well understood [2]. In this context, there is evident crucial interest in developing a new generation of devices for local magnetic recording for an in vitro system. Several recent studies have implied that MagnetoResistive (MR) technologies can detect a biological magnetic field at local scale [3,4] (i.e., brain slice, muscle in vitro). However, to date, no attempts have been carried out for neurons in culture due to the long-term biocompatibility required.In this work, we will present a platform based on MR sensors array, namely magnetic tunneling junctions (MTJs) to detect the activity of neurons in culture from a magnetic point of view. We will show the biocompatibility of our devices and the preservation of the physical properties of the sensors. Murine embryonic hippocampal neurons were grown on top of the MR sensors array. We achieve a lifetime of the on-chip neuronal networks of longer than 20 days. Neurite growth was studied during development with immunostaining analysis.In conclusion, we achieved the biocompatibility conditions of a MR platform suitable for studying the magnetic field generated by the activity of in vitro neuronal networks.