<title>Mapping neural circuits in the mammalian brain: scanning laser photostimulation in vitro</title>

Abstract

Determination of the organization, sign and strength of neuronal circuitry has resisted conventional anatomical and electrophysiological methods; it has proved particularly difficult to discretely activate isolated single circuits within the network of connections in the mammalian brain slice. Traditional electrical stimulating electrodes are poor tools for a detailed investigation of the organization of functional connections within brain slices, as they lack good spatial resolution and activate multiple neuronal circuits simultaneously. Scanning laser photostimulation offers many advantages over this and other current approaches: spatial resolution is superb, fibers of passage are not activated, and thousands of presynaptic locations can be stimulated. With this approach, caged neurotransmitters are activated in a restricted region of the brain slice by photolysis with a UV argon laser. Combining computer-controlled positioning of the laser light and whole cell recording in brain slices allows the construction of detailed maps of the position, strength, sign and number of inputs converging on a single postsynaptic neuron. We describe the technique of photostimulation, outline the instrumentation necessary to implement it, and discuss the interpretation of photostimulation- derived data. Finally, we will present examples of mapping circuits in the mammalian visual cortex using this approach. Although only recently developed, scanning laser photostimulation offers neuroscientists a powerful tool for determining the organization and function of local brain circuits.