Devices for Extracellular Detection of Astrocytic Infraslow Electrophysiological Biomarkers

Abstract

Astrocytes, a type of glial cell, actively interact with neurons and thus play a crucial role in brain information processing. This discovery, long overlooked due to the dominance of neuronal research, has prompted a significant reconsideration of their importance in understanding brain function. These cells are known from intracellular studies to exhibit low-amplitude, lowfrequency membrane potential fluctuations. Astrocytes are involved in various brain disorders and may contribute to direct current (DC) shifts. These shifts are observed during brain pathology and are considered potential electrophysiological biomarkers. To investigate the nature of astrocytes’ extracellular electrophysiology and validate the hypothesis that they contribute to the generation of DC shifts, it is crucial to develop tools capable of detecting low-amplitude infraslow electrical signals. Conventional electrodes are invaluable tools for neural electrophysiology, however, their application in astrocytes is hampered by the lower electrical excitability of these cells compared to neurons. In this thesis, organic electrochemical transistors (OECTs) made of the conjugated polymer PEDOT:PSS were developed to study astrocyte electrophysiology. The device enabled the detection of DC shifts from both mouse brain slices and rat cortical astrocyte cultures, with the signals changing upon pharmacological stimulation to induce pathological conditions such as epilepsy and ischemia. This study characterised the extracellular electrophysiology of astrocytes and demonstrated their contribution to DC shifts, potentially driven by K⁺ ion dynamics. It further elucidated the temporal relationships between DC shifts and astrocytic calcium activity, membrane potential observed through imaging, and abnormal neuronal activity. These findings demonstrate the potential of OECTs as a novel tool for studying astrocyte electrophysiology in the context of brain dysfunctions.