Department of Physiology, University of California San Francisco, San Francisco, California 94143, USA.
J Neurosci. 2012 Oct 24;32(43):15076-85. doi: 10.1523/JNEUROSCI.3128-12.2012.
The ventral tegmental area (VTA) has a central role in the neural processes that underlie motivation and behavioral reinforcement. Although thought to contain only dopamine and GABA neurons, the VTA also includes a recently discovered population of glutamate neurons identified through the expression of the vesicular glutamate transporter VGLUT2. A subset of VGLUT2(+) VTA neurons corelease dopamine with glutamate at terminals in the NAc, but others do not express dopaminergic markers and remain poorly characterized. Using transgenic mice that express fluorescent proteins in distinct cell populations, we now find that both dopamine and glutamate neurons in the medial VTA exhibit a smaller hyperpolarization-activated current (I(h)) than more lateral dopamine neurons and less consistent inhibition by dopamine D(2) receptor agonists. In addition, VGLUT2(+) VTA neurons project to the nucleus accumbens (NAc), lateral habenula, ventral pallidum (VP), and amygdala. Optical stimulation of VGLUT2(+) projections expressing channelrhodopsin-2 further reveals functional excitatory synapses in the VP as well as the NAc. Thus, glutamate neurons form a physiologically and anatomically distinct subpopulation of VTA projection neurons.
腹侧被盖区（VTA）在动机和行为强化所基于的神经过程中起着核心作用。尽管被认为仅包含多巴胺和 GABA 神经元，但 VTA 还包括最近通过囊泡谷氨酸转运体 VGLUT2 的表达而发现的一类谷氨酸能神经元。VGLUT2(+) VTA 神经元的一部分在 NAc 的末梢中共释放谷氨酸和多巴胺，但其他神经元不表达多巴胺能标记物，仍未得到充分描述。使用在不同细胞群中表达荧光蛋白的转基因小鼠，我们现在发现，内侧 VTA 中的多巴胺和谷氨酸神经元的超极化激活电流（I(h)）比更外侧的多巴胺神经元小，并且对多巴胺 D2 受体激动剂的抑制作用不那么一致。此外，VGLUT2(+) VTA 神经元投射到伏隔核（NAc）、外侧缰核、腹侧苍白球（VP）和杏仁核。表达通道视紫红质-2 的 VGLUT2(+)投射的光刺激进一步揭示了 VP 以及 NAc 中的功能性兴奋性突触。因此，谷氨酸能神经元构成了 VTA 投射神经元在生理学和解剖学上截然不同的亚群。
