High signal-to-noise, scalable and minimally invasive recording and stimulation of the nervous system in intact animals is of fundamental importance to advance the understanding of brain function. Extracellular electrodes are among the most powerful tools capable of interfacing with large neuronal populations1-3. Neuronal tissue damage remains a major limiting factor in scaling electrode arrays, and has been found to correlate with electrode diameter across different electrode materials, such as microfabricated Michigan and Utah-style arrays4, MEMS and microsystems5, soft polymer or tungsten electrodes6 and Parylene C probes7. Small diameter ultramicroelectrodes (UMEs), while highly desirable, pose significant technical challenges such as reaching sufficient electrolyte-electrode coupling and limiting stray signal loss. To overcome these challenges, we have designed juxtacellular Ultra-Low Impedance Electrodes (jULIEs), a scalable technique for achieving high signal-to-noise electrical recordings as well as stimulation with UMEs. jULIEs are metal-glass composite UMEs thermally drawn to outer diameters (OD) of <25 µm, with metal core diameters (ID) of as little as 1 µm. We introduce a two-step electrochemical modification strategy that reduces UME coupling impedances by two orders of magnitude. Modifications enabled high signal-to-noise neural recordings in vivo through wires with micrometer scale core diameters. Histological and imaging experiments indicated that local vascular damage is minimal. Spikes reached amplitudes over 1 mV in vivo, indicating that recordings are possible in close proximity to intact neurons. Recording sites can be arranged in arbitrary patterns tailored to various neuroanatomical target structures and allowing parallel penetrations. jULIEs thus represent a versatile platform that allows for reliable recording and manipulation of neural activity in any areas of the functionally intact mammalian brain.
Objective Extracellular microelectrode techniques are the most widely used approach to interrogate neuronal populations. Regardless of the manufacturing method, damage to the vasculature and circuit function during probe insertion remains a concern. Reducing the footprint of the penetrating probes is a potential solution to this issue. However, coupling to the extracellular signals requires careful surface engineering. Approach Here, we show that continuously drawn SiO2-insulated ultra-microelectrode fibres offer an attractive substrate to address these challenges. Individual fibres can be fabricated to >10m continuous stretches and a selection of diameters below 30 µm with a low resistance (<100 Ω/m), continuous metal core of <10 µm and atomically flat smooth shank surfaces. To optimize the properties of the miniaturised electrode-tissue interface, we electrodeposit rough Au structures followed by ~20nm IrOx film by electrodeposition resulting in reduction of the interfacial impedance to <500kΩ at 1 kHz. Main results We demonstrate that these ultra-low impedance electrodes (jULIEs) can record and stimulate single and multi-unit activity with minimal tissue disturbance and exceptional signal-to-noise ratio in both superficial (~40µm) and deep (~6mm) structures of the mouse brain. We further show that sensor modifications are stable and probe manufacturing is reproducible. Significance Minimally perturbing bidirectional neural interfacing can reveal circuit function in the mammalian brain in vivo.
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