A miswiring of prefrontal efferents is generally discussed by the name of "dysconnection" as the anatomical substrate of schizophrenia. Since direct histological confirmation of this hypothesis can hardly be obtained in humans, we used an animal model of schizophrenia to trace prefrontal efferents to distal cortical fields. Mongolian gerbils were intoxicated with a single high dose of methamphetamine on postnatal day 14 and reared in isolation after weaning (day 30). Controls received a saline injection and/or were reared under enriched conditions. Upon reaching adulthood (day 90), biocytin was injected into the medial prefrontal cortex into either deep or superficial laminae. The density of passing fibres and terminal fields in the frontal, parietal and insular cortices was assessed by digital image analysis. Isolation rearing or methamphetamine treatment alone reduced the projections from lamina V/VI to the frontal and from lamina III to the insular cortex, and from both laminae to the parietal cortex. In contrast, isolation rearing of methamphetamine-intoxicated gerbils significantly increased the projections from the deep laminae to the frontal and parietal cortices, compared to isolation-reared controls, with no difference in the efferents from superficial laminae. These results are the first to demonstrate a miswiring of prefrontal efferents in response to adverse systemic influences. They might give a hint at the anatomical basis of "dysconnection" in schizophrenia.

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Virtual reality (VR) environments are a powerful tool to investigate brain mechanisms involved in the behavior of animals. With this technique, animals are usually head fixed or secured in a harness, and training for cognitively more complex VR paradigms is time consuming. A VR apparatus allowing free animal movement and the constant operator-independent training of tasks would enable many new applications. Key prospective usages include brain imaging of animal behavior when carrying a miniaturized mobile device such as a fluorescence microscope or an optetrode. Here, we introduce the Servoball, a spherical VR treadmill based on the closed-loop tracking of a freely moving animal and feedback counterrotation of the ball. Furthermore, we present the complete integration of this experimental system with the animals' group home cage, from which single individuals can voluntarily enter through a tunnel with radio-frequency identification (RFID)-automated access control and commence experiments. This automated animal sorter functions as a mechanical replacement of the experimenter. We automatically trained rats using visual or acoustic cues to solve spatial cognitive tasks and recorded spatially modulated entorhinal cells. When electrophysiological extracellular recordings from awake behaving rats were performed, head fixation can dramatically alter results, so that any complex behavior that requires head movement is impossible to achieve. We circumvented this problem with the use of the Servoball in open-field scenarios, as it allows the combination of open-field behavior with the recording of nerve cells, along with all the flexibility that a virtual environment brings. This integrated home cage with a VR arena experimental system permits highly efficient experimentation for complex cognitive experiments. Virtual reality (VR) environments are a powerful tool for the investigation of brain mechanisms. We introduce the Servoball, a VR treadmill for freely moving rodents. The Servoball is integrated with the animals' group home cage. Single individuals voluntarily enter using automated access control. Training is highly time-efficient, even for cognitively complex VR paradigms.

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