Richárd Fiáth

Astrocytes convert network excitation to tonic inhibition of neurons

BackgroundGlutamate and γ-aminobutyric acid (GABA) transporters play important roles in balancing excitatory and inhibitory signals in the brain. Increasing evidence suggest that they may act concertedly to regulate extracellular levels of the neurotransmitters.ResultsHere we present evidence that glutamate uptake-induced release of GABA from astrocytes has a direct impact on the excitability of pyramidal neurons in the hippocampus. We demonstrate that GABA, synthesized from the polyamine putrescine, is released from astrocytes by the reverse action of glial GABA transporter (GAT) subtypes GAT-2 or GAT-3. GABA release can be prevented by blocking glutamate uptake with the non-transportable inhibitor DHK, confirming that it is the glutamate transporter activity that triggers the reversal of GABA transporters, conceivably by elevating the intracellular Na+ concentration in astrocytes. The released GABA significantly contributes to the tonic inhibition of neurons in a network activity-dependent manner. Blockade of the Glu/GABA exchange mechanism increases the duration of seizure-like events in the low-[Mg2+] in vitro model of epilepsy. Under in vivo conditions the increased GABA release modulates the power of gamma range oscillation in the CA1 region, suggesting that the Glu/GABA exchange mechanism is also functioning in the intact hippocampus under physiological conditions.ConclusionsThe results suggest the existence of a novel molecular mechanism by which astrocytes transform glutamatergic excitation into GABAergic inhibition providing an adjustable, in situ negative feedback on the excitability of neurons.

Two-Dimensional Multi-Channel Neural Probes With Electronic Depth Control

This paper presents multi-electrode arrays for in vivo neural recording applications incorporating the principle of electronic depth control (EDC), i.e., the electronic selection of recording sites along slender probe shafts independently for multiple channels. Two-dimensional (2D) arrays were realized using a commercial 0.5- μm complementary-metal-oxide-semiconductor (CMOS) process for the EDC circuits combined with post-CMOS micromachining to pattern the comb-like probes and the corresponding electrode metallization. A dedicated CMOS integrated front-end circuit was developed for pre-amplification and multiplexing of the neural signals recorded using these probes.

In Vivo Measurements With Robust Silicon-Based Multielectrode Arrays With Extreme Shaft Lengths

In this paper, manufacturing and in vivo testing of extreme-long Si-based neural microelectrode arrays are presented. Probes with different shaft lengths (15-70 mm) are formed by deep reactive ion etching and have been equipped with platinum electrodes of various configurations. In vivo measurements on rats indicate good mechanical stability, robust implantation, and targeting capability. High-quality signals have been recorded from different locations of the cerebrum of the rodents. The accompanied tissue damage is characterized by histology.

Two-dimensional multi-channel neural probes with electronic depth control

Multi-electrode arrays for in vivo neural recording are presented incorporating the principle of electronic depth control, i.e. an electronic selection of electrode locations along the probe shaft independently for multiple channels. Two-dimensional (2D) arrays are realized using a commercial CMOS process for the electronic circuits combined with post-CMOS micromachining for shaping the probes and electrode metallization. These 2D arrays can be further assembled into 3D arrays. Two-dimensional arrays with IrO x metal finish show electrode impedances between 100 KΩ and 1 MΩ. In vivo tests demonstrate the capability to simultaneously record multi-unit activity in addition to local field potentials on all 32 available output channels of the probe combs. Electronic steering enabled some of the electrodes to record from cortical and others to record from thalamic sites in the rat. This new device significantly increases the amount of useful information that can be obtained from a single experiment.

In vivo validation of the electronic depth control probes

Abstract In this article, we evaluated the electrophysiological performance of a novel, high-complexity silicon probe array. This brain-implantable probe implements a dynamically reconfigurable voltage-recording device, coordinating large numbers of electronically switchable recording sites, referred to as electronic depth control (EDC). Our results show the potential of the EDC devices to record good-quality local field potentials, and single- and multiple-unit activities in cortical regions during pharmacologically induced cortical slow wave activity in an animal model.

Time Multiplexed Active Neural Probe with 1356 Parallel Recording Sites

We present a high electrode density and high channel count CMOS (complementary metal-oxide-semiconductor) active neural probe containing 1344 neuron sized recording pixels (20 µm × 20 µm) and 12 reference pixels (20 µm × 80 µm), densely packed on a 50 µm thick, 100 µm wide, and 8 mm long shank. The active electrodes or pixels consist of dedicated in-situ circuits for signal source amplification, which are directly located under each electrode. The probe supports the simultaneous recording of all 1356 electrodes with sufficient signal to noise ratio for typical neuroscience applications. For enhanced performance, further noise reduction can be achieved while using half of the electrodes (678). Both of these numbers considerably surpass the state-of-the art active neural probes in both electrode count and number of recording channels. The measured input referred noise in the action potential band is 12.4 µVrms, while using 678 electrodes, with just 3 µW power dissipation per pixel and 45 µW per read-out channel (including data transmission).

A Multimodal, SU-8-Platinum - Polyimide Microelectrode Array for Chronic In Vivo Neurophysiology

Utilization of polymers as insulator and bulk materials of microelectrode arrays (MEAs) makes the realization of flexible, biocompatible sensors possible, which are suitable for various neurophysiological experiments such as in vivo detection of local field potential changes on the surface of the neocortex or unit activities within the brain tissue. In this paper the microfabrication of a novel, all-flexible, polymer-based MEA is presented. The device consists of a three dimensional sensor configuration with an implantable depth electrode array and brain surface electrodes, allowing the recording of electrocorticographic (ECoG) signals with laminar ones, simultaneously. In vivo recordings were performed in anesthetized rat brain to test the functionality of the device under both acute and chronic conditions. The ECoG electrodes recorded slow-wave thalamocortical oscillations, while the implanted component provided high quality depth recordings. The implants remained viable for detecting action potentials of individual neurons for at least 15 weeks.

Tunable Low Noise Amplifier Implementation With Low Distortion Pseudo-Resistance for in Vivo Brain Activity Measurement

This paper presents a low power neural signal amplifier with tunable cut-off frequencies. The presented compact amplifier, which is used for sensing various types of neural signals, reduces the size and the power consumption of the whole circuit. The distinguishing features of this solution are the large time constant, linearity, and small achievable area, which are realized with a configurable series of pseudo resistances. The proof of concept has been manufactured on TSMC 90 nm technology.

Hybrid intracerebral probe with integrated bare LED chips for optogenetic studies

This article reports on the development, i.e., the design, fabrication, and validation of an implantable optical neural probes designed for in vivo experiments relying on optogenetics. The probes comprise an array of ten bare light-emitting diode (LED) chips emitting at a wavelength of 460 nm and integrated along a flexible polyimide-based substrate stiffened using a micromachined ladder-like silicon structure. The resulting mechanical stiffness of the slender, 250-μm-wide, 65-μm-thick, and 5- and 8-mm-long probe shank facilitates its implantation into neural tissue. The LEDs are encapsulated by a fluropolymer coating protecting the implant against the physiological conditions in the brain. The electrical interface to the external control unit is provided by 10-μm-thick, highly flexible polyimide cables making the probes suitable for both acute and chronic in vivo experiments. Optical and electrical properties of the probes are reported, as well as their in vivo validation in acute optogenetic studies in transgenic mice. The depth-dependent optical stimulation of both excitatory and inhibitory neurons is demonstrated by altering the brain activity in the cortex and the thalamus. Local network responses elicited by 20-ms-long light pulses of different optical power (20 μW and 1 mW), as well as local modulation of single unit neuronal activity to 1-s-long light pulses with low optical intensity (17 μW) are presented. The ability to modulate neural activity makes these devices suitable for a broad variety of optogenetic experiments.

FPGA-based neural probe positioning to improve spike sorting with OSort algorithm

The extracellular measurement of brain electrical activity contains local field potentials and mixtures of action potentials generated by the neurons. It is essential to determine which individual neuron produces the recorded unit activity, so spike sorting methods are used. High channel-count neural probes are capable of recording the activity of large neural ensembles from up to more than hundred individual brain positions simultaneously, pose an even greater challenge for spike sorting applied on general-purpose hardware. Real-time clinical applications could greatly benefit from a hardware-accelerated data processing, especially in the case of Field-Programmable Gate Arrays (FPGAs) or Application Specific Integrated Circuits (ASICs), which are energy-efficient compared to traditional CPUs or GPUs, and can significantly reduce the computation time required to process large amounts of high-dimensional data. In this paper, we present a real-time FPGA-based implementation of a multi-channel Online Sorting (OSort) algorithm to pre-cluster neural data. Based on this pre-processing the neurobiologists can fine-tune the position of neural probe and improve the efficiency of offline spike sorting.