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.