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Altered Cortical Glutamate Neurotransmission in Schizophrenia
Evidence from Morphological Studies of Pyramidal Neurons
Departments of aPsychiatry and bNeuroscience, University of Pittsburgh, Pennsylvania 15213, USA cDepartment of Psychiatry, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599, USA
Address for correspondence: David A. Lewis, M.D., Department of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, W1651 BST, Pittsburgh, PA 15213. Voice: 412-624-3934; fax: 412-624-9910. lewisda{at}msx.upmc.edu Ann. N.Y. Acad. Sci. 1003: 102-112 (2003).
Multiple lines of evidence from pharmacological, neuroimaging, and postmortem studies implicate disturbances in cortical glutamate neurotransmission in the pathophysiology of schizophrenia. Given that pyramidal neurons are the principal source of cortical glutamate neurotransmission, as well as the targets of the majority of cortical glutamate-containing axon terminals, understanding the nature of altered glutamate neurotransmission in schizophrenia requires an appreciation of both the types of pyramidal cell abnormalities and the specific class(es) of pyramidal cells that are affected in the illness. In this chapter, we review evidence indicating that a subpopulation of pyramidal neurons in the dorsolateral prefrontal cortex exhibits reductions in dendritic spine density, a marker of the number of excitatory inputs, and in somal volume, a measure correlated with a neuron's dendritic and axonal architecture. Specifically, pyramidal neurons located in deep layer 3 of the dorsolateral prefrontal cortex and that lack immunoreactivity for nonphosphorylated neurofilament protein may be particularly involved in the pathophysiology of schizophrenia. The presence of similar changes in pyramidal neurons located in deep layer 3 of auditory association cortex suggests that a shared property, which remains to be determined, confers cell type-specific vulnerability to a subpopulation of cortical glutamatergic neurons in schizophrenia.
Key Words: schizophrenia • pyramidal neurons • dorsolateral prefrontal cortex • deep layer 3 This article has been cited by other articles:
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