Active Stabilization of Electrodes for Intracellular Recording in Awake Behaving Animals

Intracellular recording is a powerful electrophysiology technique that has revealed much of what is known about the biophysical properties of neurons. However, neuronal properties are strongly affected by activity dependent and modulatory influences, making it essential, ultimately, to study these properties in behaving animals. Unfortunately, intracellular recording has only been widely applied in vitro, since cardiac and respiratory pulsations make intracellular recording difficult in vivo. In awake behaving animals, spontaneous movements make intracellular recording nearly impossible. Here I present a novel technique to dynamically stabilize the position of a recording electrode relative to the brain. Physiological signals that are predictive of brain motion at the recording site, such as the electrocardiogram (EKG), respiratory pressure, or cranial motion, are used to control a piezoelectric manipulator, making possible stable intracellular recordings in awake active animals.