Abstract

In vivo electrophysiological recordings from groups of distinguishable neurons in behaving mice is a technique with a rapidly growing appeal, particularly because it can be combined with gene targeting techniques. This methodology is deemed essential for achieving a flexible and versatile coupling of molecular-genetic manipulations with behavioral and system level analyses of the nervous system. One major obstacle in obtaining this technological integration is the relatively high weight and bulk size of the available implantable devices for ensemble recordings as compared to the size of the animal. This imposes considerable physical stress on the animals and may prevent them from performing complex behavioral tasks for more than a few minutes. We developed a novel micro-drive which allows independent day-to-day positioning of up to 6 tetrodes in the mouse brain, with an extremely reduced weight and size. The system is based on an “exoskeleton” as its structural element, and allows a completely rectilinear path of the electrodes inside the drive and into the brain. Tests showed that mice can tolerate the chronically implanted device very well up to 12 weeks after implantation, while exhibiting normal behavior. Cell yields and stability obtained with this drive in two different brain areas (the hippocampus and orbitofrontal cortex) were comparable to those of traditional recording systems, usually applied to rats. The device may greatly expand possibilities to combine gene targeting and ensemble recording techniques, in behaviorally varied as well as cognitively demanding settings.

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