title: Glutamatergic gene expression is specifically reduced in thalamocortical projecting relay neurons in schizophrenia.
abstract: BACKGROUND
  Impairment of glutamate neurons that relay sensory and cognitive information from the medial dorsal thalamus to the dorsolateral prefrontal cortex and other cortical regions may contribute to the pathophysiology of schizophrenia. In this study, we have assessed the cell-specific expression of glutamatergic transcripts in the medial dorsal thalamus.
  
  
  METHODS
  We used laser capture microdissection to harvest two populations of medial dorsal thalamic cells, one enriched with glutamatergic relay neurons and the other with gamma-aminobutyric acidergic neurons and astroglia, from postmortem brains of subjects with schizophrenia (n = 14) and a comparison group (n = 20). Quantitative polymerase chain reaction of extracted RNA was used to assay gene expression in the different cell populations.
  
  
  RESULTS
  The transcripts encoding the ionotropic glutamate receptor subunits NR2D, GluR3, GluR6, GluR7, and the intracellular proteins GRIP1 and SynGAP1 were significantly decreased in relay neurons but not in the mixed glial and interneuron population in schizophrenia.
  
  
  CONCLUSIONS
  Our data suggest that reduced ionotropic glutamatergic expression occurs selectively in neurons, which give rise to the cortical projections of the medial dorsal thalamus in schizophrenia, rather than in thalamic cells that function locally. Our findings indicate that glutamatergic innervation is dysfunctional in the circuitry between the medial dorsal thalamus and cortex.
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama, USA. mssodhi@uic.edu
authors.forename: Monsheel S
authors.initials: MS
authors.lastname: Sodhi
authors.forename: Micah
authors.initials: M
authors.lastname: Simmons
authors.forename: Robert
authors.initials: R
authors.lastname: McCullumsmith
authors.forename: Vahram
authors.initials: V
authors.lastname: Haroutunian
authors.forename: James H
authors.initials: JH
authors.lastname: Meador-Woodruff
mesh_terms: D002352:Carrier Proteins / Q000096:biosynthesis; D002540:Cerebral Cortex / Q000378:metabolism*; D059330:GABAergic Neurons / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007395:Interneurons / Q000378:metabolism; D061346:Laser Capture Microdissection / Q000379:methods; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009434:Neural Pathways / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D017470:Receptors, Glutamate / Q000096:biosynthesis*; D012559:Schizophrenia / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000096:biosynthesis
chemical_list: D002352:Carrier Proteins; C491310:GRIP1 protein, human; D009419:Nerve Tissue Proteins; D017470:Receptors, Glutamate; C484739:SYNGAP1 protein, human; D020703:ras GTPase-Activating Proteins