Background The axons of chandelier cells (ChCs) target the axon initial segment (AIS) of pyramidal neurons, forming an array of boutons termed a cartridge. In schizophrenia, the density of cartridges detectable by GABA membrane transporter-1 (GAT1) immunoreactivity is lower, whereas the density of AISs detectable by immunoreactivity for the α2 subunit of the GABA-A receptor is higher in layers 2-superficial 3 of the prefrontal cortex (PFC). These findings were interpreted as compensatory responses to lower GABA levels in ChCs. However, we recently found that in schizophrenia ChC cartridge boutons contain normal levels of the 67 kDa isoform of glutamic acid decarboxylase (GAD67) protein, the enzyme responsible for GABA synthesis in these boutons. To understand these findings we quantified the densities of ChC cartridges immunoreactive for vesicular GABA transporter (vGAT+), which is present in all cartridge boutons, and the subset of cartridges that contain calbindin (CB+). Methods PFC tissue sections from 20 matched pairs of schizophrenia and unaffected comparison subjects were immunolabeled for vGAT, GAD67, and CB. Results The mean density of vGAT+/CB+ cartridges was 2.7-fold higher, exclusively in layer 2 of schizophrenia subjects, whereas the density of vGAT+/CB− cartridges did not differ between subject groups. Neither vGAT, CB, or GAD67 protein levels per ChC bouton, nor the number of boutons per cartridge, differed between subject groups. Conclusions Our findings of a greater density of CB+ ChC cartridges in PFC layer 2 from schizophrenia subjects suggests that the normal developmental pruning of these cartridges is blunted in the illness.

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Several postmortem studies have reported lower levels of immunoreactivity (IR) for microtubule-associated protein 2 (MAP2) in several cortical regions of individuals with schizophrenia (SZ). However, whether this effect is conserved across multiple brain areas within an individual with SZ or if it is regionally-specific remains unclear. We characterized patterns of MAP2-IR across three cortical regions at different levels of the rostral-caudal axis within individual subjects with and without SZ. MAP2-IR levels were measured in deep layer 3 of dorsolateral prefrontal cortex (DLPFC), lateral intraparietal cortex (LIP), and primary visual cortex (V1). Postmortem tissue containing each cortical region was derived from 20 pairs of SZ subjects and nonpsychiatric comparison (NPC) subjects matched perfectly for sex, and as closely as possible for age and postmortem interval. MAP2-IR was assessed by quantitative fluorescence microscopy. We observed significantly lower levels of MAP2-IR in SZ subjects relative to NPC subjects, without a significant region by diagnosis interaction. Logs of the within-pair ratios (SZ:NPC) of MAP2-IR were significantly correlated across the three regions. These findings demonstrate that MAP2-IR deficits in SZ are consistent across three neocortical regions within individual subjects. This pattern of MAP2-IR deficit has implications for therapeutic development and future investigations of MAP2 pathology in SZ.