Synchronized activation of striatal direct and indirect pathways underlies the behavior in unilateral dopamine-depleted mice

Synchronized activation of striatal direct and indirect pathways underlies the behavior in unilateral dopamine-depleted mice
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DOI:
10.1111/ejn.14344
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发表时间:
2019-06-01
影响因子:
3.4
通讯作者:
Arbuthnott, Gordon William
Arbuthnott, Gordon William
中科院分区:
医学3区
文献类型:
--
作者:
Jaidar, Omar;Carrillo-Reid, Luis;Arbuthnott, Gordon William

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For more than three decades it has been known, that striatal neurons become hyperactive after the loss of dopamine input, but the involvement of dopamine (DA) D1- or D2-receptor-expressing neurons has only been demonstrated indirectly. By recording neuronal activity using fluorescent calcium indicators in D1 or D2 eGFP-expressing mice, we showed that following dopamine depletion, both types of striatal output neurons are involved in the large increase in neuronal activity generating a characteristic cell assembly of particular neurons that dominate the pattern. When we expressed channelrhodopsin in all the output neurons, light activation in freely moving animals, caused turning like that following dopamine loss. However, if the light stimulation was patterned in pulses the animals circled in the other direction. To explore the neuronal participation during this stimulation we infected normal mice with channelrhodopsin and calcium indicator in striatal output neurons. In slices made from these animals, continuous light stimulation for 15 s induced many cells to be active together and a particular dominant group of neurons, whereas light in patterned pulses activated fewer cells in more variable groups. These results suggest that the simultaneous activity of a large dominant group of striatal output neurons is intimately associated with parkinsonian symptoms.