A 256Ã\x97256 CMOS Microelectrode Array for Extracellular Neural Stimulation of Acute Brain Slices

Extracellular stimulation of neurons is an important tool in investigating the function of the nervous system. Optical techniques, based on voltage- and calcium-sensitive dyes or photouncaging, along with multi-photon fluorescent microscopy have proven very successful in imaging activity in slices and in vivo. However, studies have been limited by the ability to stimulate different regions of tissue with enough spatial resolution and throughput. Traditional stimulation is accomplished with passive multielectrode arrays (MEAs) or bipolar electrodes. In both cases, a relatively small number of stimulation sites with coarse spatial resolution are possible. While there has been recent work on the development of CMOS chips for extracellular recordings of cultured neurons or slices on planar electrodes, the focus of this work is on stimulation and achieving stable electrical interfaces between acute slices and a high-density active CMOS MEA. As brain slices preserve many synaptic connections, they are ideal preparations to study neuronal microcircuits in vitro. Active stimulation technologies should enable detailed "reverse engineering" of neural circuitry.