Abstract
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.
Highlights
In the isocortex PVIs mainly comprise basket and chandelier cells, which control network activity by targeting the soma and proximal dendrites or the axon initial segment of principal cells, respectively[25]
Local field potential (LFP) recordings from prefrontal cortex (PFC) showed no indication of enhanced synchronous activity in PFC-PV-TeLC mice
As deficits in working memory are a dominant cognitive symptom in both schizophrenia and PFC lesions[4,35,38,39] we investigated the involvement of PVIs in the production of working memory
Summary
In the isocortex PVIs mainly comprise basket and chandelier cells, which control network activity by targeting the soma and proximal dendrites or the axon initial segment of principal cells, respectively[25]. They are well placed to exert rigorous control over PFC activity. To distinguish PFC-dependent behaviors which require intact PVI signaling from those that do not, we compared PVI-selective interference with non-cell-type-selective perturbations of the same circuitry in behavioral assays that were chosen to detect alterations that map onto symptom categories (positive, negative, cognitive) in schizophrenia
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