Effects of a mediodorsal thalamus lesion on prefrontal inhibitory circuitry: implications for schizophrenia.
BACKGROUND
Schizophrenia is associated with both reductions in prefrontal cortical (PFC) inhibitory markers and in neuron number in the mediodorsal thalamus (MDTN), which provides excitatory input to the PFC. To investigate the potential pathophysiologic relationship between these observations, we sought to provide experimental evidence that a reduction in MDTN neurons can produce decreased PFC glutamate decarboxylase (GAD(67)) mRNA expression.


METHODS
Ibotenic acid was injected bilaterally into MDTN in rats. Four weeks later, thalamic lesion volumes were assessed stereologically, and PFC GAD(67) mRNA expression was measured using in situ hybridization.


RESULTS
Selective MDTN lesions produced no changes in PFC GAD(67) mRNA expression, either overall or by cortical layer, and lesion volumes and GAD(67) mRNA expression were not correlated.


CONCLUSIONS
In rats, a substantial lesion of MDTN neurons does not decrease PFC GAD(67) mRNA expression. These results do not support the hypothesis that decreased PFC GAD(67) mRNA expression in schizophrenia is attributable to a reduction in MDTN neuron number.
Volk
David W
DW
Department of Neuroscience, University of Pittsburgh, Pennsylvania 15213, USA.
Lewis
David A
DA
D000818:Animals; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D007051:Ibotenic Acid / Q000633:toxicity; D017403:In Situ Hybridization / Q000379:methods; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D009044:Motor Cortex / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000503:physiopathology*; D013788:Thalamus / Q000473:pathology* / Q000503:physiopathology
D018690:Excitatory Amino Acid Agonists; D007527:Isoenzymes; D012333:RNA, Messenger; D007051:Ibotenic Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1