Cellular and Synaptic Morphology of Golgi -Impregnated Cortical Neurons in Patients With Schizophrenia

Several postmortem studies of schizophrenia reveal that despite normal numbers of cortical neurons, patients exhibit anatomical reductions in synaptic connectivity. Prefrontal regions have been implicated as a site of vulnerability to pathophysiological alterations, while evidence of anatomical disturbances in other cortical regions points to more distributed changes. Our studies investigated whether schizophrenia is associated with anatomical alterations in the postsynaptic targets of prefrontal pyramidal neurons: dendrites and dendritic spines, and whether these alterations differ across brain region, cortical layer, cell type, or antipsychotic treatments. Formalin-fixed tissue blocks from frontopolar cortex, Area 10, and primary visual cortex, Area 17, were acquired from a pool of 16 subjects with chronic schizophrenia and 22 normal comparison subjects. Golgi-impregnated pyramidal neurons from Layer 3 and Layer 5 were systematically randomly sampled and reconstructed, and measures of somal area, basilar dendritic length, spine density, and spine morphology were used for comparisons. Schizophrenia diagnosis was associated with significant reductions in basilar dendrites of pyramidal neurons in Layers 3 and 5 from both cortical regions. Both regions also exhibited significant shifts in spine morphologies on Layer 3 pyramidal basilar dendrites, suggesting distributed abnormalities in synaptic number and structure in schizophrenia. However, Area 10 exhibited selective reductions in Layer 3 pyramidal neuron spine density and somal area, as well as more severe dendritic reductions in both layers, suggesting that prefrontal neurons may be more affected in schizophrenia. Furthermore, pilot studies suggest that these changes do not appear to result from antipsychotic exposure or cohort effects.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Kodish, Ian Michael

Contributors dc:contributor

• Greenough, William T.

• Health Sciences, Mental Health

Language dc:language

eng

Identifier

(MiAaPQ)AAI3153354

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/82499