Abstract
Studies on information processing and learning properties of neuronal networks would benefit from simultaneous and parallel access to the activity of a large fraction of all neurons in such networks. Here, we present a CMOS-based device, capable of simultaneously recording the electrical activity of over a thousand cells in in vitro neuronal networks. The device provides sufficiently high spatiotemporal resolution to enable, at the same time, access to neuronal preparations on subcellular, cellular, and network level. The key feature is a rapidly reconfigurable array of 26 400 microelectrodes arranged at low pitch (17.5 μm) within a large overall sensing area (3.85 × 2.10 mm(2)). An arbitrary subset of the electrodes can be simultaneously connected to 1024 low-noise readout channels as well as 32 stimulation units. Each electrode or electrode subset can be used to electrically stimulate or record the signals of virtually any neuron on the array. We demonstrate the applicability and potential of this device for various different experimental paradigms: large-scale recordings from whole networks of neurons as well as investigations of axonal properties of individual neurons.
Highlights
To understand how neuronal networks perform informationprocessing tasks, such as information storage and learning, it is desirable to have means to simultaneously record the electrical activity of many single neurons and to stimulate defined neurons at the same time
We demonstrate that the complementary metaloxide-semiconductor (CMOS)-based HD-microelectrode arrays (MEAs) presented here is well suited to accommodate such different preparations in that it allows for selection of the most suitable electrodes for a particular experiment
We presented a CMOS based high-density MEA (HD-MEA) capable of, at the same time, recording from neuronal networks with hundreds of cells as well as of capturing subtle subcellular signal details from the axonal arbor of single neurons
Summary
To understand how neuronal networks perform informationprocessing tasks, such as information storage and learning, it is desirable to have means to simultaneously record the electrical activity of many single neurons and to stimulate defined neurons at the same time. A different class of MEAs, based on complementary metaloxide-semiconductor (CMOS) technology, has been developed to address some of these issues.[12,13,14,15,16,17] By integrating circuitry on the same substrate as the recording electrodes, CMOS MEAs can overcome some of the inherent limitations of passive MEAs. Most importantly, CMOS MEAs allow for overcoming the connectivity problem so that thousands of microelectrodes can be arranged at high spatial resolution through using multiplexing techniques, whereby electronic switches are employed to access shared signal wires. CMOS MEAs allow for overcoming the connectivity problem so that thousands of microelectrodes can be arranged at high spatial resolution through using multiplexing techniques, whereby electronic switches are employed to access shared signal wires This approach drastically reduces the number of required interconnections between electrodes and amplifiers, allowing for a more effective use of available routing area. By integrating the amplifiers and analog-to-digital converters (ADCs) on the same substrate as the electrodes, the number of off-chip connections can be reduced, since the digitized signals can be sent off-chip sequentially through only a small number of
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