title: Intracortical excitatory and thalamocortical boutons are intact in primary auditory cortex in schizophrenia.
abstract: Schizophrenia is associated with auditory processing impairments that could arise as a result of primary auditory cortex excitatory circuit pathology. We have previously reported a deficit in dendritic spine density in deep layer 3 of primary auditory cortex in subjects with schizophrenia. As boutons and spines can be structurally and functionally co-regulated, we asked whether the densities of intracortical excitatory or thalamocortical presynaptic boutons are also reduced. We studied 2 cohorts of subjects with schizophrenia and matched controls, comprising 27 subject pairs, and assessed the density, number, and within-bouton vesicular glutamate transporter (VGluT) protein level of intracortical excitatory (VGluT1-immunoreactive) and thalamocortical (VGluT2-immunoreactive) boutons in deep layer 3 of primary auditory cortex using quantitative confocal microscopy and stereologic sampling methods. We found that VGluT1- and VGluT2-immunoreactive puncta densities and numbers were not altered in deep layer 3 of primary auditory cortex of subjects with schizophrenia. Our results indicate that reduced dendritic spine density in primary auditory cortex of subjects with schizophrenia is not matched by a corresponding reduction in excitatory bouton density. This suggests excitatory boutons in primary auditory cortex in schizophrenia may synapse with structures other than spines, such as dendritic shafts, with greater frequency. The discrepancy between dendritic spine reduction and excitatory bouton preservation may contribute to functional impairments of the primary auditory cortex in subjects with schizophrenia.
authors.affiliation: Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Moyer
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Delevich
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Fish
authors.forename: Josephine K
authors.initials: JK
authors.lastname: Asafu-Adjei
authors.forename: Allan R
authors.initials: AR
authors.lastname: Sampson
authors.forename: Karl-Anton
authors.initials: KA
authors.lastname: Dorph-Petersen
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
mesh_terms: D000328:Adult; D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016022:Case-Control Studies; D015331:Cohort Studies; D003712:Dendrites / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D016014:Linear Models; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology*; D011569:Psychiatric Status Rating Scales; D011877:Radionuclide Imaging; D012559:Schizophrenia / Q000473:pathology*; D016708:Synaptophysin / Q000378:metabolism; D013788:Thalamus / Q000473:pathology*; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: C493476:SLC17A6 protein, human; C493464:SLC17A7 protein, human; D016708:Synaptophysin; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2
keywords: Postmortem human tissue; Primary auditory cortex; Quantitative microscopy; Stereology; VGluT1; VGluT2