Sullivan Matthew A, Chen Huanmian, Morikawa Hitoshi
Waggoner Center for Alcohol and Addiction Research, Section of Neurobiology and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, USA.
J Neurosci. 2008 Aug 27;28(35):8682-90. doi: 10.1523/JNEUROSCI.2411-08.2008.
The striatum plays a central role in sensorimotor learning and action selection. Tonically active cholinergic interneurons in the striatum give rise to dense axonal arborizations and significantly shape striatal output. However, it is not clear how the activity of these neurons is regulated within the striatal microcircuitry. In this study, using rat brain slices, we find that stimulation of intrastriatal cholinergic fibers evokes polysynaptic GABA(A) IPSCs in cholinergic interneurons. These polysynaptic GABA(A) IPSCs were abolished by general nicotinic acetylcholine receptor antagonists and also by a specific antagonist of nicotinic receptors containing beta2 subunits. Dopamine receptor antagonists or dopamine depletion failed to block polysynaptic IPSCs, indicating that phasic dopamine release does not directly mediate the polysynaptic transmission. Dual recording from pairs of cholinergic interneurons revealed that activation of a single cholinergic interneuron is capable of eliciting polysynaptic GABA(A) IPSCs both in itself and in nearby cholinergic interneurons. Although polysynaptic transmission arising from a single cholinergic interneuron was depressed during repetitive 2 Hz firing, intrastriatal stimulation reliably evoked large polysynaptic IPSCs by recruiting many cholinergic fibers. We also show that polysynaptic GABAergic inhibition leads to a transient suppression of tonic cholinergic interneuron firing. We propose a novel microcircuit in the striatum, in which cholinergic interneurons are connected to one another through GABAergic interneurons. This may provide a mechanism to convert activation of cholinergic interneurons into widespread recurrent inhibition of these neurons via nicotinic excitation of striatal GABAergic neurons.
纹状体在感觉运动学习和动作选择中起核心作用。纹状体内持续活跃的胆碱能中间神经元会产生密集的轴突分支，并显著塑造纹状体输出。然而，尚不清楚这些神经元的活动在纹状体微回路中是如何被调节的。在本研究中，我们使用大鼠脑片发现，刺激纹状体内胆碱能纤维可在胆碱能中间神经元中诱发多突触GABA(A)抑制性突触后电流（IPSCs）。这些多突触GABA(A) IPSCs被一般的烟碱型乙酰胆碱受体拮抗剂以及含有β2亚基的烟碱型受体特异性拮抗剂所消除。多巴胺受体拮抗剂或多巴胺耗竭未能阻断多突触IPSCs，这表明多巴胺的阶段性释放并不直接介导多突触传递。对成对胆碱能中间神经元进行双记录显示，单个胆碱能中间神经元的激活能够在其自身以及附近的胆碱能中间神经元中诱发多突触GABA(A) IPSCs。尽管在2 Hz重复放电期间，单个胆碱能中间神经元产生的多突触传递受到抑制，但纹状体内刺激通过募集许多胆碱能纤维可靠地诱发了大的多突触IPSCs。我们还表明，多突触GABA能抑制导致胆碱能中间神经元的紧张性放电出现短暂抑制。我们提出了一种纹状体中的新型微回路，其中胆碱能中间神经元通过GABA能中间神经元相互连接。这可能提供了一种机制，通过纹状体GABA能神经元的烟碱样兴奋，将胆碱能中间神经元的激活转化为对这些神经元的广泛反馈抑制。
