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right © 2020 the authors.Piccolo, a presynaptic active zone protein, is best known for its role in the regulated assembly and function of vertebrate synapses. Genetic studies suggest a further link to several psychiatric disorders as well as Pontocerebellar Hypoplasia type 3 (PCH3). We have characterized recently generated Piccolo knockout (Pclogt/gt ) rats. Analysis of rats of both sexes revealed a dramatic reduction in brain size compared to wildtype (Pclowt/wt ) animals, attributed to a decrease in the size of the cerebral cortical,