EXCEED THE SPACE PROVIDED. Recent studies have directed attentionto the thalamus in schizophrenia. Many of those _;tudieshave focused on the mediodorsal thalamic nucleus because of itsconnections with the dorsola:_erapl refrontal cortex, a brain region consistentlyimplicated in schizophrenia. In addition to the mediodnrsal nucleus, our recent neuroimaging and postmortem histologicalstudies have implicated another thalamic nucleus, the pulvinar, in the diathesis of the disorder. We have found the pulvinar of schizophrenics to be reduced in volume and neuronal number relative to the pulvinar of normal subjects. The pulvinar is a complex nucleus comprising five subnuclei, each with a unique set of connections with other brain egions. Understanding which of its subnuclei are affected in schizophrenia is crucial to understanding how schizophrenia impairs communication among various brain regions.
We aim to determine which of the subnuclei are characterized by changes in volume and neuronal number. This work must be carried out on postmortem brain material because these subnuclei cannot be seen in brain scans of living subjects. We will use computer-assisted morphometric techniques to measure the volume of each subnucleus in 12 schizophrenic subjects and 12 nonschizophrenic comparison subjects. We will also count the number of neurons in each subnucleus. In addition, will use immunocytochemistry for the calcium binding proteins, parvalbumin and calbindin, to identify neurons that project out of the thalamus to the cortex as opposed to neurons that remain in the thalmaus or project to noncortical regions. We predict that volume and neuron loss will primarily affect the medial subnucleus of the pulvinar because of its connections with other brain regions implicated in schizophrenia, and because it is believed to play a role in a variety of functions that are impaired in schizophrenia including language, selective attention, and saccadic eye movements. Atrophic changes have been described in schizophrenic cortex and hypothesized to be secondary to a lack of excitatory input. Because thalamocortical neurons provide excitatory input to cortex, we hypothesize that the pulvinar of schizophrenics will exhibit a deficit of cortically projecting neurons identified by immunostaining for parvalbumin and calbindin. PERFORMANCE SITE ========================================Section End===========================================

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Special Emphasis Panel (ZRG1-BDCN-6 (01))
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Meinecke, Douglas L
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Mount Sinai School of Medicine
Schools of Medicine
New York
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Barley, Kevin; Dracheva, Stella; Byne, William (2009) Subcortical oligodendrocyte- and astrocyte-associated gene expression in subjects with schizophrenia, major depression and bipolar disorder. Schizophr Res 112:54-64
Byne, William; Hazlett, Erin A; Buchsbaum, Monte S et al. (2009) The thalamus and schizophrenia: current status of research. Acta Neuropathol 117:347-68
Byne, William; Tatusov, Alex; Yiannoulos, Georgia et al. (2008) Effects of mental illness and aging in two thalamic nuclei. Schizophr Res 106:172-81
Byne, William; Fernandes, Jason; Haroutunian, Vhram et al. (2007) Reduction of right medial pulvinar volume and neuron number in schizophrenia. Schizophr Res 90:71-5
Byne, William; Kidkardnee, Smith; Tatusov, Alex et al. (2006) Schizophrenia-associated reduction of neuronal and oligodendrocyte numbers in the anterior principal thalamic nucleus. Schizophr Res 85:245-53