Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, 12800 E 19th Ave, Aurora, CO 80045, USA.
Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, 12800 E 19th Ave, Aurora, CO 80045, USA.
Cell Rep. 2022 May 17;39(7):110823. doi: 10.1016/j.celrep.2022.110823.
Substantia nigra pars compacta (SNc) dopamine neurons play a key role in regulating the activity of striatal circuits within the basal ganglia. In addition to dopamine, these neurons release several other transmitters, including the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Both dopamine and GABA are loaded into SNc synaptic vesicles by the vesicular monoamine transporter 2 (VMAT2), and co-release of GABA provides strong inhibition to the striatum by directly inhibiting striatal medium spiny projection neurons (MSNs) through activation of GABA receptors. Here, we found that despite both dopamine and GABA being co-packaged by VMAT2, the properties of transmission, including Ca sensitivity, release probability, and requirement of active zone scaffolding proteins, differ between the two transmitters. Moreover, the extent by which presynaptic neuromodulators inhibit co-transmission also varied. Differences in modulation and the mechanisms controlling release allow for independent regulation of dopamine and GABA signals despite both being loaded via similar mechanisms.
黑质致密部 (SNc) 多巴胺神经元在调节基底神经节内纹状体回路的活动中起着关键作用。除了多巴胺，这些神经元还释放其他几种递质，包括主要的抑制性神经递质γ-氨基丁酸（GABA）。囊泡单胺转运体 2（VMAT2）将多巴胺和 GABA 都装载到 SNc 突触小泡中，GABA 的共释放通过激活 GABA 受体直接抑制纹状体，从而对纹状体产生强烈抑制作用。在这里，我们发现尽管多巴胺和 GABA 都被 VMAT2 共包装，但两种递质的传递特性，包括钙敏感性、释放概率和活性区支架蛋白的需求，存在差异。此外，突触前神经调质抑制共传递的程度也不同。释放的调节和控制机制的差异允许尽管多巴胺和 GABA 信号都通过类似的机制加载，但仍可以独立调节。
