Schizophrenia (SZ) is often described as a disease of neuronal connectivity. Cognitive processes such as working memory, which are particularly dependent on the proper functioning of complex cortical circuitry, are disturbed in the disease. Reciprocal connections between pyramidal neurons and interneurons, as well as dopaminergic innervations, form the basis for higher cognition in the cortex. Nonetheless, only a few review articles are available which address how each synapse operates, and is possibly disturbed in SZ, at least in part by the mechanisms involving genetic susceptibility factors for SZ. In this review, we provide an overview of cortical glutamatergic, GABAergic, and dopaminergic circuitry, review SZ-associated deficits at each of these synapses, and discuss how genetic factors for SZ may contribute to SZ-related phenotype deficits in a synapse-specific manner. Pinpointing the spatially and temporally distinct sites of action of putative SZ susceptibility factors may help us better understand the pathological mechanisms of SZ, especially those associated with synaptic functioning and neuronal connectivity.
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