Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models
Michelle Day, Zhongfeng Wang, Jun Ding, Xinhai An, Cali A Ingham, Andrew F Shering, David Wokosin, Ema Ilijic, Zhuoxin Sun, Allan R Sampson, Enrico Mugnaini, Ariel Y Deutch, Susan R Sesack,Gordon W Arbuthnott & D James Surmeier
Nature neuroscience (2006)
doi:10.1038/nn1632
The gap/question: how the activity of medial spiny neurons in the striatum were changed after dopamine depletion?
How the authors proposed the question: Parkinson’s diseases were accompanied by severe motor deficits, which was associated with cell death of dopamine neurons. Because midbrain dopamine neurons strongly projected to the striatum, influential theory proposed that the death of dopamine neurons caused the imbalance of the direct-/striatonigral/D1-MSNs and indirect-/striatopallidal-/D2-MSNs pathways within the striatum, which led to a series of motor deficits. Limited by the tools to specifically target different cell types, no studies had directly dissect the dopamine depletion effects on the D1- and D2- MSNs. This study was the first attempt to tackle this question with newly developed genetic tools. So this study is type which used new techniques to solve the old questions.
Brief summary: by using BAC genetic labeling methods, the authors shown that the depletion of dopamine neurons specifically eliminated the spines and glutamatergic synapses on D2-MSNs, but not on D1-MSNs, in the striatum. It suggested the the disconnection between corticostriatal inputs to D2-MSNs may be neural substrates of pathologies observed in Parkinson’s disease.
The most striking findings in this study was the specific effects on D2-MSNs after dopamine depletion. Based on brain slice recording, the authors found that the firing rates of D2-MSNs also decreased. This observation was inconsistent with the conventional view about D2-MSNs’ role in suppressing behavioral responses. Intuitively, decreased D2-MSNs’ activity would lead to enhanced behavioral responses, which was the opposite to the phenotypes of Parkinson’s patients. The results indicated that it was much more complex than a linear up-and-down story. The key point is how the imbalanced activity of D1- and D2- MSNs affects the outputs of basal ganglia and the down-stream brain areas.
