Dysfunction of parvalbumin (PV)-positive GABAergic interneurons (PVIs) within the prefrontal cortex (PFC) has been implicated in schizophrenia pathology. It is however unclear, how impaired signaling of these neurons may contribute to PFC dysfunction. To identify how PVIs contribute to PFC-dependent behaviors we inactivated PVIs in the PFC in mice using region- and cell-type-selective expression of tetanus toxin light chain (TeLC) and compared the functional consequences of this manipulation with non-cell-type-selective perturbations of the same circuitry. By sampling for behavioral alterations that map onto distinct symptom categories in schizophrenia, we show that dysfunction of PVI signaling in the PFC specifically produces deficits in the cognitive domain, but does not give rise to PFC-dependent correlates of negative or positive symptoms. Our results suggest that distinct aspects of the complex symptomatology of PFC dysfunction in schizophrenia can be attributed to specific prefrontal circuit elements.

In recent years recombinant adeno-associated viral vectors (AAV) have become increasingly valuable for in vivo studies in animals, and are also currently being tested in human clinical trials. Wild-type AAV is a non-pathogenic member of the parvoviridae family and inherently replicationdeficient. The broad transduction profile, low immune response as well as the strong and persistent transgene expression achieved with these vectors has made them a popular and versatile tool for in vitro and in vivo gene delivery. rAAVs can be easily and cheaply produced in the laboratory and, based on their favourable safety profile, are generally given a low safety classification. Here, we describe a method for the production and titering of chimeric rAAVs containing the capsid proteins of both AAV1 and AAV2. The use of these so-called chimeric vectors combines the benefits of both parental serotypes such as high titres stocks (AAV1) and purification by affinity chromatography (AAV2). These AAV serotypes are the best studied of all AAV serotypes, and individually have a broad infectivity pattern. The chimeric vectors described here should have the infectious properties of AAV1 and AAV2 and can thus be expected to infect a large range of tissues, including neurons, skeletal muscle, pancreas, kidney among others. The method described here uses heparin column purification, a method believed to give a higher viral titer and cleaner viral preparation than other purification methods, such as centrifugation through a caesium chloride gradient. Additionally, we describe how these vectors can be quickly and easily titered to give accurate reading of the number of infectious particles produced.

Humans, even babies, perceive causality when one shape moves briefly and linearly after another. Motion timing is crucial in this and causal impressions disappear with short delays between motions. However, the role of temporal information is more complex: it is both a cue to causality and a factor that constrains processing. It affects ability to distinguish causality from non-causality, and social from mechanical causality. Here we study both issues with 3- to 7-year-olds and adults who saw two computer-animated squares and chose if a picture of mechanical, social or non-causality fit each event best. Prior work fit with the standard view that early in development, the distinction between the social and physical domains depends mainly on whether or not the agents make contact, and that this reflects concern with domain-specific motion onset, in particular, whether the motion is self-initiated or not. The present experiments challenge both parts of this position. In Experiments 1 and 2, we showed that not just spatial, but also animacy and temporal information affect how children distinguish between physical and social causality. In Experiments 3 and 4 we showed that children do not seem to use spatio-temporal information in perceptual causality to make inferences about self- or other-initiated motion onset. Overall, spatial contact may be developmentally primary in domain-specific perceptual causality in that it is processed easily and is dominant over competing cues, but it is not the only cue used early on and it is not used to infer motion onset. Instead, domain-specific causal impressions may be automatic reactions to specific perceptual configurations, with a complex role for temporal information.

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