Title:Region-Specific Dendritic Spine Loss of Pyramidal Neurons in Dopamine Transporter Knockout Mice
Volume: 15
Issue: 3
Author(s): Y. Kasahara, Y. Arime, F.S. Hall, G.R. Uhl and I. Sora
Affiliation:
关键词:
杏仁基底外侧核，树突，GFP转基因老鼠，海马体，内侧前额叶皮质，运动皮质，椎体细胞，树突棘密度
摘要: 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.
