Center For Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, New Jersey 07102, USA.
J Neurosci. 2010 May 19;30(20):6999-7016. doi: 10.1523/JNEUROSCI.5996-09.2010.
Whole-cell recordings were obtained from tyrosine hydroxylase-expressing (TH(+)) neurons in striatal slices from bacterial artificial chromosome transgenic mice that synthesize enhanced green fluorescent protein (EGFP) selectively in neurons expressing TH transcriptional regulatory sequences. Stereological cell counting indicated that there were approximately 2700 EGFP-TH(+) neurons/striatum. Whole-cell recordings in striatal slices demonstrated that EGFP-TH(+) neurons comprise four electrophysiologically distinct neuron types whose electrophysiological properties have not been reported previously in striatum. EGFP-TH(+) neurons were identified in retrograde tracing studies as interneurons. Recordings from synaptically connected pairs of EGFP-TH(+) interneurons and spiny neurons showed that the interneurons elicited GABAergic IPSPs/IPSCs in spiny neurons powerful enough to significantly delay evoked spiking. EGFP-TH(+) interneurons responded to local or cortical stimulation with glutamatergic EPSPs. Local stimulation also elicited GABA(A) IPSPs, at least some of which arose from identified spiny neurons. Single-cell reverse transcription-PCR showed expression of VMAT1 in EGFP-TH(+) interneurons, consistent with previous suggestions that these interneurons may be dopaminergic as well as GABAergic. All four classes of interneurons were medium sized with modestly branching, varicose dendrites, and dense, highly varicose axon collateral fields. These data show for the first time that there exists in the normal rodent striatum a substantial population of TH(+)/GABAergic interneurons comprising four electrophysiologically distinct subtypes whose electrophysiological properties differ significantly from those of previously described striatal GABAergic interneurons. These interneurons are likely to play an important role in striatal function through fast GABAergic synaptic transmission in addition to, and independent of, their potential role in compensation for dopamine loss in experimental or idiopathic Parkinson's disease.
从细菌人工染色体转基因小鼠的纹状体切片中获得了表达酪氨酸羟化酶（TH(+)）的神经元的全细胞记录，这些转基因小鼠选择性地在表达 TH 转录调节序列的神经元中合成增强型绿色荧光蛋白（EGFP）。立体细胞计数表明，每个纹状体中有大约 2700 个 EGFP-TH(+)神经元。纹状体切片中的全细胞记录表明，EGFP-TH(+)神经元包括四种电生理学上不同的神经元类型，其电生理特性以前在纹状体中没有报道过。在逆行追踪研究中，EGFP-TH(+)神经元被鉴定为中间神经元。从突触连接的 EGFP-TH(+)中间神经元和棘神经元对记录显示，中间神经元在棘神经元中引起足够强大的 GABA 能 IPSP/IPSCs，足以显著延迟诱发的放电。EGFP-TH(+)中间神经元对局部或皮质刺激产生谷氨酸能 EPSPs。局部刺激也引起 GABA(A) IPSPs，其中至少一些来自已识别的棘神经元。单细胞逆转录-PCR 显示 EGFP-TH(+)中间神经元表达 VMAT1，这与先前的观点一致，即这些中间神经元可能既是多巴胺能的，也是 GABA 能的。所有四种中间神经元均为中等大小，具有适度分支、多棘突的树突和密集、高度多棘突的轴突侧支场。这些数据首次表明，在正常的啮齿动物纹状体中存在大量的 TH(+)/GABA 能中间神经元，它们包括四种电生理学上不同的亚型，其电生理特性与以前描述的纹状体 GABA 能中间神经元有显著差异。这些中间神经元可能通过快速 GABA 能突触传递在纹状体功能中发挥重要作用，除了它们在实验性或特发性帕金森病中补偿多巴胺缺失的潜在作用之外。
