Dual Dopaminergic Regulation of Corticostriatal Plasticity by Cholinergic Interneurons and Indirect Pathway Medium Spiny Neurons.
Dual Dopaminergic Regulation of Corticostriatal Plasticity by Cholinergic Interneurons and Indirect Pathway Medium Spiny Neurons.
复制标题
DOI：
10.1016/j.celrep.2018.08.042
复制
发表时间：
2018-09-11
期刊：
影响因子：
8.8
通讯作者：
Lovinger DM
中科院分区：
文献类型：
--
作者：
Augustin SM;Chancey JH;Lovinger DM
内源性大麻素（Endocannabinoid，eCB）介导的长期抑郁（long-term depression，LTD）需要多巴胺（dopamine，DA）D2受体（dopamine，D2 Rs）来动员eCB。参与LTD诱导的D2 R的细胞位点仍然存在高度争议。我们使用神经元特异性靶向缺失D2 Rs直接检测了纹状体胆碱能中间神经元（Chls）和间接通路中型棘神经元（iMSNs）表达的D2 Rs在LTD诱导中的作用。Chl-D2 Rs的缺失（Chl-Drd 2KO）损害了MSN的两种亚型中的LTD诱导。M1选择性毒蕈碱乙酰胆碱受体拮抗剂恢复了Chl-Drd 2KO小鼠的LTD诱导。相比之下，在iMSN-D2 R（iMSN-Drd 2KO）缺失后，LTD诱导在MSN中是完整的。直接途径和iMSNs的单独询问揭示了LTD诱导的缺陷，仅在缺乏D2 R的iMSNs上的syn-apses处。通过D2 R激动剂应用恢复iMSN中的LTD诱导。我们的研究结果表明，Chl D2 Rs强烈调节MSN中的LTD诱导，iMSN-D2 Rs具有较弱的iMSN特异性调节作用。多巴胺D2受体（D2 Rs）参与皮质纹状体长时程突触抑制（LTD）的细胞定位存在争议。Augustin等人表明，胆碱能中间神经元上的D2 R强烈调节突触处的LTD诱导到所有中等多刺神经元（MSN）上，而iMSN上的D2 R微弱调节突触处的诱导到iMSN上。
Endocannabinoid (eCB)-mediated long-term depres-sion (LTD) requires dopamine (DA) D2 receptors (D2Rs) for eCB mobilization. The cellular locus of the D2Rs involved in LTD induction remains highly debated. We directly examined the role in LTD induc-tion of D2Rs expressed by striatal cholinergic inter-neurons (Chls) and indirect pathway medium spiny neurons (iMSNs) using neuron-specific targeted deletion of D2Rs. Deletion of Chl-D2Rs (Chl-Drd2KO) impaired LTD induction in both subtypes of MSNs. LTD induction was restored in the Chl-Drd2KO mice by an M1-selective muscarinic acetylcholine receptor antagonist. In contrast, after the deletion of iMSN-D2Rs (iMSN-Drd2KO), LTD induction was intact in MSNs. Separate interrogation of direct pathway and iMSNs revealed a deficit in LTD induction only at syn-apses onto iMSNs that lack D2Rs. LTD induction in iMSNs was restored by D2R agonist application. Our findings suggest that Chl D2Rs strongly modulate LTD induction in MSNs, with iMSN-D2Rs having a weaker, iMSN-specific, modulatory effect. The cellular location of dopamine D2 receptors (D2Rs) involved in corticostriatal long-term synaptic depression (LTD) is controversial. Augustin et al. show that D2Rs on cholinergic interneurons strongly modulate LTD induction at synapses onto all medium spiny neurons (MSNs), while D2Rs on iMSNs weakly modulate nduction at synapses onto iMSNs.
登录
查看更多内容
影响因子：
8.8
作者：
Beeler JA;Frank MJ;McDaid J;Alexander E;Turkson S;Bernardez Sarria MS;McGehee DS;Zhuang X
通讯作者：
Zhuang X
影响因子：
25
作者：
Giuffrida, A;Parsons, LH;Piomelli, D
通讯作者：
Piomelli, D
影响因子：
25
作者：
Gerdeman, GL;Ronesi, J;Lovinger, DM
通讯作者：
Lovinger, DM
影响因子：
5.3
作者：
Bamford, NS;Robinson, S;Meshul, CK
通讯作者：
Meshul, CK
影响因子：
56.9
作者：
GERFEN, CR;ENGBER, TM;SIBLEY, DR
通讯作者：
SIBLEY, DR