Department of Neurobiology and Behavior, Center for Nervous System Disorders, Stony Brook University School of Medicine, Stony Brook, NY 11794, USA.
Interdisciplinary Program in Neuroscience, George Mason University, Fairfax, VA 22030, USA.
Neuron. 2020 Dec 23;108(6):1091-1102.e5. doi: 10.1016/j.neuron.2020.09.028. Epub 2020 Oct 19.
Corticostriatal synaptic integration is partitioned among striosome (patch) and matrix compartments of the dorsal striatum, allowing compartmentalized control of discrete aspects of behavior. Despite the significance of such organization, it's unclear how compartment-specific striatal output is dynamically achieved, particularly considering new evidence that overlap of afferents is substantial. We show that dopamine oppositely shapes responses to convergent excitatory inputs in mouse striosome and matrix striatal spiny projection neurons (SPNs). Activation of postsynaptic D1 dopamine receptors promoted the generation of long-lasting synaptically evoked "up-states" in matrix SPNs but opposed it in striosomes, which were more excitable under basal conditions. Differences in dopaminergic modulation were mediated, in part, by dendritic voltage-gated calcium channels (VGCCs): pharmacological manipulation of L-type VGCCs reversed compartment-specific responses to D1 receptor activation. These results support a novel mechanism for the selection of striatal circuit components, where fluctuating levels of dopamine shift the balance of compartment-specific striatal output.
皮质纹状体突触整合在背侧纹状体的纹状体（斑块）和基质隔室中进行分区，从而可以对行为的离散方面进行分区控制。尽管这种组织具有重要意义，但尚不清楚如何动态实现特定隔室的纹状体输出，尤其是考虑到新的证据表明传入纤维的重叠是很大的。我们表明，多巴胺以相反的方式塑造了对小鼠纹状体和基质纹状体棘突投射神经元（SPN）中会聚兴奋性输入的反应。激活突触后 D1 多巴胺受体可促进基质 SPN 中持久的突触诱发“上状态”的产生，但在纹状体中则相反，纹状体在基础条件下更易兴奋。多巴胺能调制的差异部分由树突电压门控钙通道（VGCC）介导：L 型 VGCC 的药理学操纵可逆转 D1 受体激活的隔室特异性反应。这些结果支持了一种选择纹状体电路组件的新机制，其中多巴胺的波动水平改变了特定隔室纹状体输出的平衡。
