多巴胺缺失后快速靶向特异性重塑快速发射抑制性回路。

Rapid target-specific remodeling of fast-spiking inhibitory circuits after loss of dopamine.

机构信息

Gladstone Institute of Neurological Disease, University of California, San Diego, La Jolla, CA 92093, USA.

出版信息

Neuron. 2011 Sep 8;71(5):858-68. doi: 10.1016/j.neuron.2011.06.035.

DOI:10.1016/j.neuron.2011.06.035

PMID:21903079

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3170520/

Abstract

In Parkinson's disease (PD), dopamine depletion alters neuronal activity in the direct and indirect pathways and leads to increased synchrony in the basal ganglia network. However, the origins of these changes remain elusive. Because GABAergic interneurons regulate activity of projection neurons and promote neuronal synchrony, we recorded from pairs of striatal fast-spiking (FS) interneurons and direct- or indirect-pathway MSNs after dopamine depletion with 6-OHDA. Synaptic properties of FS-MSN connections remained similar, yet within 3 days of dopamine depletion, individual FS cells doubled their connectivity to indirect-pathway MSNs, whereas connections to direct-pathway MSNs remained unchanged. A model of the striatal microcircuit revealed that such increases in FS innervation were effective at enhancing synchrony within targeted cell populations. These data suggest that after dopamine depletion, rapid target-specific microcircuit organization in the striatum may lead to increased synchrony of indirect-pathway MSNs that contributes to pathological network oscillations and motor symptoms of PD.

摘要

在帕金森病（PD）中，多巴胺耗竭改变了直接和间接通路中的神经元活动，并导致基底神经节网络中的同步性增加。然而，这些变化的起源仍然难以捉摸。由于 GABA 能中间神经元调节投射神经元的活动并促进神经元同步，我们在多巴胺耗竭后用 6-OHDA 从纹状体快速放电（FS）中间神经元和直接或间接通路 MSN 对进行了记录。FS-MSN 连接的突触特性仍然相似，然而，在多巴胺耗竭后的 3 天内，单个 FS 细胞将其与间接通路 MSN 的连接性增加了一倍，而与直接通路 MSN 的连接性保持不变。纹状体微电路的模型表明，FS 支配的这种增加在增强靶向细胞群体内的同步性方面是有效的。这些数据表明，在多巴胺耗竭后，纹状体中快速的、针对特定目标的微电路组织可能导致间接通路 MSN 的同步性增加，这有助于 PD 病理性网络振荡和运动症状的产生。