To begin to make a bridge from neuron cell culture to the brain, our lab has worked for several years to develop a culture system in which multiple neurons can grow into a network, with each cell independently addressable. We call this a "neurochip". Each neuron is "caged" over an electrode that can be used for extracellular stimulation and recording without damaging the cell. Dissociated neurons grow axons and dendrites out through tunnels of the cages and connect to form rich networks. By stimulating each cell and recording the responses of all the others, the connectivity of the network can be followed over time. After three weeks, a culture may have over 100 connections, with each neuron on average driving half of the others. Collecting data such as this has never before been possible. We are ready to capitalize on this ability by studying central questions of brain network development.|
In vivo, ongoing background neural activity promotes network maturation in many brain regions, and we will explore that effect. We will stimulate neurochip neurons individually at uncorrelated times while the cultures grow, at physiologically relevant rates. In addition, a very important role of activity is modifying synaptic connectivity for learning and memory, by enhancement or reduction of synaptic strength as a result of paired-pulse stimulation. Pairs of cells in our networks will be used to study this learning, not just for minutes as in the previous experiments, but for long times, with chronic stimulation of cultures while they develop. See www.caltech.edu/~pinelab. Contact: Jerry Pine at firstname.lastname@example.org.
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