Bioelectronic devices to measure astrocyte-neuron communication

Bioelectronic devices fabricated  with bacterial cellulose and PEDOT:PSS AstroNeuroCircuit Astrocyte-Neuron network
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AstroNeuroCircuit

Project Funded by Fundação para Ciência e Tecnologia (FCT)

Ref. 2022.06979.PTDC

Abstract

Currently available, in vitro, neurotechnologies to study the brain are essentially focused on neuron-neuron communication. However, the latest research in the area has highlighted the importance of another class of brain cells, called astrocytes. Astrocytes are highly complex cells that can bi-directionally regulate the information processing of synapses, controlling and reconfiguring the flow of information in neuronal networks. According to recent findings, a single astrocyte can control several thousands of synapses. This evidence has caused a paradigm shift in our understanding of brain activity. It is now accepted that neuron– astrocyte interaction plays a critical role in the processing of information, computation, and memory. Dysfunctional interaction between neurons and astrocytes lead to neurodegenerative disorders. A growing body of evidence also suggests that astrocyte-astrocyte connectivity and astrocyte-neuron connectivity has to be considered together with the standard neuron–neuron connectivity to understand how the brain works.

Until now neuro-astrocyte communication has not been measured using extracellular devices because astrocytes are fundamentally different from neurons. Action potentials fired by individual neurons are signals with duration of milliseconds traveling through the axon at speeds of meters per second. In contrast, astrocytes are cooperative cells that synchronize their activity to generate calcium waves that propagate across the biological tissue at speed of just a few microns per second. The timescales at which neurons and astrocytes work are impressively different; signals generated by astrocytes are typically one million times slower than an action potential. This huge temporal difference imposes experimental requirements very different from the ones encountered in state-ofartelectrophysiological techniques to study neuronal communication. Microelectrode array technology, known as MEAs, which is currently available to study neuron-neuron communication, is blind to extracellular signals generated by astrocytes. In addition, traditional patch-clamp methods are invasive, and optical fluorometric methods use dyes and light sources which disturb the physiological functions and limit the observation to a few hours In this view, the demand for electrical-based technologies that can target and both selectively monitor, and control astrocytes is emerging as a challenge across neuroscience, electrical engineering, and materials science. Novel technologies are urgently required to measure the ultra-low frequency and weak signals generated by astrocytes.

Our team pioneered the first devices to measure extracellular signals generated by populations of astrocytes and demonstrated that these homogenous astrocyte populations generate signals that can last from 2 to 10 seconds, and the signal period can be as long as 10 minutes. To achieve that we used a large area and nanostructured surface.

Relying on our previous knowledge, the goal of this proposal is to build a novel and disruptive sensing interface that simultaneously can measure both the faint low-frequency signals generated by Astrocytes together with the fast action potentials generated by the neurons in a neuron-astrocyte communicating network.

To individually address both types of cellular networks as well as the astro-neuron network, we propose an innovative co-culture chamber where both astrocytes and neurons populations can meet and establish a neuronal circuit. This system will be equipped with an array of electrical sensing surfaces spatially distributed and geometrically optimized to selectively collect and discriminate the different bioelectrical signals generated by the two types of cells. To overcome the challenge imposed by 1/f type noise and to increase the signal-to-noise ratio (SNR) we propose to use organic conducting polymer coatings deposited on nanostructured surfaces to offer a low impedance interface and a soft 3D-like environment to the adherent cells.