Dual Control of Dopamine Synthesis and Release by Presynaptic and Postsynaptic Dopamine D2 Receptors
Dual Control of Dopamine Synthesis and Release by Presynaptic and Postsynaptic Dopamine D2 Receptors
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DOI：
10.1523/jneurosci.0918-12.2012
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发表时间：
2012-06-27
影响因子：
5.3
通讯作者：
Borrelli, Emiliana
中科院分区：
文献类型：
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作者：
Anzalone, Andrea;Lizardi-Ortiz, Jose E.;Borrelli, Emiliana
多巴胺能稳态失调导致多巴胺(DA)水平低或高与帕金森氏症、精神分裂症和成瘾有因果关系。DA合成的主要部位是起源于黑质和腹侧被盖区的中脑神经元；这些结构分别向背侧纹状体(DST)和伏核(NAcc)发出主要投射。DA通过激活DAD2受体(D2R)微调自己的合成和释放。到目前为止，这一关键的D2R依赖功能被认为完全是由于D2R在多巴胺能神经元(D2自身受体)上的激活；相反，使用特定部位的D2R基因敲除小鼠，我们发现位于非DAR能介质的棘神经元上的D2异源受体参与了DA水平的控制。这种D2异源受体介导的机制在DST中比在NAcc中更有效，表明D2R信号对中边缘和黑质纹状体介导的功能有不同的调节作用。这项研究揭示了以前不为人知的对DA信号的控制，为DA介导的效应的区域特异性调控提供了新的线索。
Dysfunctions of dopaminergic homeostasis leading to either low or high dopamine (DA) levels are causally linked to Parkinson's disease, schizophrenia, and addiction. Major sites of DA synthesis are the mesencephalic neurons originating in the substantia nigra and ventral tegmental area; these structures send major projections to the dorsal striatum (DSt) and nucleus accumbens (NAcc), respectively. DA finely tunes its own synthesis and release by activating DAD2 receptors (D2R). To date, this critical D2R-dependent function was thought to be solely due to activation of D2Rs on dopaminergic neurons (D2 autoreceptors); instead, using site-specific D2R knock-out mice, we uncover that D2 heteroreceptors located on non-DAergic medium spiny neurons participate in the control of DA levels. This D2 heteroreceptor-mediated mechanism is more efficient in the DSt than in NAcc, indicating that D2R signaling differentially regulates mesolimbic-versus nigrostriatal-mediated functions. This study reveals previously unappreciated control of DA signaling, shedding new light on region-specific regulation of DA-mediated effects.