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腺苷A2A受体对新纹状体抑制性网络中棘状投射神经元突触连接的作用。

Actions of adenosine A 2A receptors on synaptic connections of spiny projection neurons in the neostriatal inhibitory network.

作者信息

Shindou Tomomi, Arbuthnott Gordon W, Wickens Jeffery R

机构信息

Department of Anatomy and Structural Biology, University of Otago, Dunedin, New Zealand.

出版信息

J Neurophysiol. 2008 Apr;99(4):1884-9. doi: 10.1152/jn.01259.2007. Epub 2008 Feb 13.

Abstract

There is growing evidence that adenosine plays a crucial role in basal ganglia function, particularly in the modulation of voluntary movement. An adenosine-based treatment for Parkinson's disease shows promise in recent clinical studies. Adenosine A(2A) receptors, the receptors involved in this treatment, are highly expressed in the neostriatum. Previous studies have suggested opposing actions of these receptors on synaptic transmission at striatal and pallidal terminals of the same spiny projection neurons, but the cells of origin of the intrastriatal terminals mediating these actions have not been identified. We used dual whole cell recordings to record simultaneously from pairs of striatal cells; this enabled definitive identification of the presynaptic and postsynaptic cells mediating the effects of A(2A) receptors. We found that A(2A) receptors facilitate GABAergic synaptic transmission by intrastriatal collaterals of the spiny projection neurons, consistent with their previously reported actions on synaptic transmission at pallidal terminals. This neuromodulatory action on lateral inhibition in the striatum may underlie, in part, the therapeutic efficacy of adenosine-based treatments for Parkinson's disease.

摘要

越来越多的证据表明,腺苷在基底神经节功能中起着关键作用,尤其是在对自主运动的调节方面。基于腺苷的帕金森病治疗方法在最近的临床研究中显示出前景。参与这种治疗的腺苷A(2A)受体在新纹状体中高度表达。先前的研究表明,这些受体对同一棘状投射神经元的纹状体和苍白球终末的突触传递具有相反的作用,但介导这些作用的纹状体内终末的起源细胞尚未确定。我们使用双全细胞记录法同时记录成对的纹状体细胞;这使得能够明确鉴定介导A(2A)受体作用的突触前和突触后细胞。我们发现,A(2A)受体通过棘状投射神经元的纹状体内侧支促进GABA能突触传递,这与它们先前报道的对苍白球终末突触传递的作用一致。这种对纹状体侧向抑制的神经调节作用可能部分解释了基于腺苷的帕金森病治疗方法的治疗效果。

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