Advances in Network Electrophysiology Using Multi-Electrode Arrays, pp. 215-242. Taketani, M. and Baudry, M. New York, Springer

For certain key functions, simple animals use large identified neurons, such as the locust's Giant Motion Detector neuron (LGMD), which integrates visual information and triggers jumping (Gabbiani et al., 1999). By contrast, in the vertebrate nervous system, individual neurons are probably not important; each function is subserved by many nerve cells working in concert. However, we have little understanding of how single-unit activity combines to form the network-level processing that takes in sensory input, stores memories, and controls behavior. Cultured neuronal networks have provided us with much of our present understanding of ion channels, receptor molecules, and synaptic plasticity that may form the basis of learning and memory (Bi and Poo, 1998; Latham et al., 2000; Misgeld et al., 1998; Muller et al., 1992; Ramakers et al., 1991). To study the nervous system in vitro offers many advantages over in vivo approaches. In vitro systems are much more accessible to microscopic imaging and pharmacological manipulation than are intact animals. Recent developments in multi-electrode array (MEA) technology, including those described below, will enable researchers to answer questions not just at the single-neuron level, but at the network level. Most MEA research has involved recording the activity that cultured networks produce spontaneously, via up to 64 extracellular electrodes. While some studies also included electrical stimulation via the substrate electrodes, it was applied to only one or two of them at a time (Connolly et al., 1990; Fromherz and Stett, 1995; Gross et al., 1993; Jimbo and Kawana, 1992; Jimbo et al., 1998; Maeda et al., 1995; Oka et al., 1999; Regehr et al., 1989; Shahaf and Marom, 2001; Stoppini et al., 1997). We propose that in order to substantially advance our understanding of network dynamics, we need high-bandwidth (many neuron) communication in both directions, out of and into the network. This chapter describes technologies that allow recording and stimulation on every electrode of an MEA, and a new closed-loop paradigm that brings in vitro research into the behavioral realm.