Diagnostic Specificity and Association With Cognition of Molecular Alterations in Prefrontal Somatostatin Neurons in Schizophrenia.

Importance: Individuals with schizophrenia (SZ) exhibit pronounced deficits in somatostatin (SST) messenger RNA (mRNA) levels in the dorsolateral prefrontal cortex (DLPFC). Molecularly distinct subtypes of SST neurons, located in the superficial and deep zones of the DLPFC, are thought to contribute to different functional processes of this region; understanding the specificity of SST alterations in SZ across these zones could inform the functional consequences of those alterations, including cognitive impairments characteristic of SZ.

Objective: To quantify mRNA levels of SST and related neuropeptides in the DLPFC in individuals with SZ, bipolar disorder (BPD), or major depressive disorder (MDD) and unaffected comparison individuals.

Localization and Diagnostic Specificity of Glutamic Acid Decarboxylase Transcript Alterations in the Dorsolateral Prefrontal Cortex in Schizophrenia.

Background: Working memory (WM) deficits in schizophrenia are thought to reflect altered inhibition in the dorsolateral prefrontal cortex (DLPFC). This interpretation is supported by findings of lower transcript levels of the 2 enzymes, GAD67 and GAD65, which mediate basal and activity-dependent GABA (gamma-aminobutyric acid) synthesis, respectively. However, the relative magnitude, location within the depth of the DLPFC, and specificity to the disease process of schizophrenia of alterations in GAD67 and/or GAD65 remain unclear.

Distinct Laminar and Cellular Patterns of GABA Neuron Transcript Expression in Monkey Prefrontal and Visual Cortices.

The functional output of a cortical region is shaped by its complement of GABA neuron subtypes. GABA-related transcript expression differs substantially between the primate dorsolateral prefrontal cortex (DLPFC) and primary visual (V1) cortices in gray matter homogenates, but the laminar and cellular bases for these differences are unknown. Quantification of levels of GABA-related transcripts in layers 2 and 4 of monkey DLPFC and V1 revealed three distinct expression patterns: 1) transcripts with higher levels in DLPFC and layer 2 [e.

Postnatal Development of Glutamate and GABA Transcript Expression in Monkey Visual, Parietal, and Prefrontal Cortices.

Visuospatial working memory (vsWM) requires information transfer among multiple cortical regions, from primary visual (V1) to prefrontal (PFC) cortices. This information is conveyed via layer 3 glutamatergic neurons whose activity is regulated by gamma-aminobutyric acid (GABA)ergic interneurons. In layer 3 of adult human neocortex, molecular markers of glutamate neurotransmission were lowest in V1 and highest in PFC, whereas GABA markers had the reverse pattern.

Distinct Properties of Layer 3 Pyramidal Neurons from Prefrontal and Parietal Areas of the Monkey Neocortex.

In primates, working memory function depends on activity in a distributed network of cortical areas that display different patterns of delay task-related activity. These differences are correlated with, and might depend on, distinctive properties of the neurons located in each area. For example, layer 3 pyramidal neurons (L3PNs) differ significantly between primary visual and dorsolateral prefrontal (DLPFC) cortices.