We propose to develop a revolutionary tool for simultaneous intracellular recording from hundreds of
single neurons in the freely-moving animal. In order to link neural activity and behavior it is essential to
record the electrical activity of many individual neurons simultaneously for long periods of time. Current
methods allow recording of multiple neurons only at the spike level, losing the crucial details that are available
in subthreshold synaptic activity. Intracellular recordings in awake freely moving animals has been achieved
only a handful of times, one neuron at a time and for very brief periods.
Here we propose a novel approach for solving this problem by developing in vivo multielectrode array (MEA)
platforms that implement the IN-CELL recording approach - using extracellular electrodes to provide
intracellular signals – which we have developed and demonstrated using in vitro systems.
The groundbreaking bioengineering process underlying the IN-CELL recording approach consists of "luring"
neurons to tightly engulf micrometric sized gold mushroom-shaped microelectrode (gMµE) functionalized by
bioactive materials. This unique design enables the formation of a tight seal resistance by the cleft between the
neuron's plasma membrane and the gMµE “neck”, together with an increased conductance of the junctional
membrane that faces the gMµE. The configuration enables effective intracellular recordings and stimulation
and, in in vitro systems, is stable over long periods of time (weeks).
Our unique design, experience and know-how, along with the most advanced concepts and technologies
developed by the international bioengineering community for flexible in vivo MEA platforms, will be used to
develop, manufacture, test and apply in vivo MEAs carrying gMµEs that match the recording and
stimulation qualities of intracellular microelectrodes and will be used for acute or chronic recordings of the
entire electrophysiological repertoire. The technology will be scalable and allow recordings from hundreds of
individual neurons in multiple brain regions.