title: Region-specific dendritic spine loss of pyramidal neurons in dopamine transporter knockout mice.
abstract: Dopamine transporter (DAT) knockout (KO) mice show numerous behavioral alterations, including hyperlocomotion, cognitive deficits, impulsivity and impairment of prepulse inhibition of the startle reflex (PPI), phenotypes that may be relevant to frontostriatal disorders such as schizophrenia. Dendritic spine changes of pyramidal neurons in the dorsolateral prefrontal cortex (DLPFC) are among the most replicated of findings in postmortem studies of schizophrenia. The mechanisms that account for dendritic changes in the DLPFC in schizophrenia are unclear. Here, we report basal spine density of pyramidal neurons in the medial prefrontal cortex (mPFC), the motor cortex, the CA1 region of the hippocampus, and the basolateral amygdala in DAT KO mice. Pyramidal neurons were visualized using DAT KO mice crossbred with a Thy1-GFP transgenic mouse line. We observed a significant decrease in spine density of pyramidal neurons in the mPFC and the CA1 region of the hippocampus in DAT KO mice compared to that in WT mice. On the other hand, no difference was observed in spine density of pyramidal neurons in the motor cortex or the basolateral amygdala between DAT genotypes. These results suggest that decreased spine density could cause hypofunction of the mPFC and the hippocampus, and contribute to the behavioral abnormalities observed in DAT KO mice, including cognitive deficits. This might suggest that aberrant dopaminergic signaling may trigger dystrophic changes in dendrites of hippocampal and prefrontocortical pyramidal neurons in schizophrenia.
authors.forename: Y
authors.initials: Y
authors.lastname: Kasahara
authors.forename: Y
authors.initials: Y
authors.lastname: Arime
authors.forename: F S
authors.initials: FS
authors.lastname: Hall
authors.forename: G R
authors.initials: GR
authors.lastname: Uhl
authors.affiliation: Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. sora@med.tohoku.ac.jp.
authors.forename: I
authors.initials: I
authors.lastname: Sora
mesh_terms: D000679:Amygdala / Q000473:pathology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000473:pathology; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D005260:Female; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009044:Motor Cortex / Q000473:pathology; D009928:Organ Specificity; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology*; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins