Postmortem structural studies of the thalamus in schizophrenia.

In this review, we seek to answer the following question: Do findings in the current literature support the idea that thalamo-cortical dysfunction in schizophrenia is due to structural abnormalities in the thalamus? We base our review on the existing literature of design-unbiased stereological studies of the postmortem thalamus from subjects with schizophrenia. Thus, all reported results are based upon the use of unbiased principles of sampling to determine volume and/or total cell numbers of thalamus or its constituent nuclei. We found 28 such papers covering 26 studies. In a series of tables we list all positive and negative findings from the total thalamus, the mediodorsal, pulvinar and anterior nuclei, as well as less frequently studied thalamic regions. Only four studies examined the entire thalamus and the results were inconsistent. We found largely consistent evidence for structural changes (reduced volume and cell numbers) in the pulvinar located in the posterior thalamus. In contrast, findings in the mediodorsal thalamic nucleus are inconsistent, with the largest and most recent studies generally failing to support earlier reports of a lower number of neurons in schizophrenia. Thus, the current findings of stereological studies of the thalamus in schizophrenia support the idea that thalamo-cortical dysfunction in schizophrenia might be attributable, at least in part, to structural alterations in the pulvinar that could impair thalamic inputs to higher order cortical association areas in the frontal and parietal lobes. However, more studies are needed before robust conclusions can be drawn.

Intracortical excitatory and thalamocortical boutons are intact in primary auditory cortex in schizophrenia.

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.