Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory
Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory
复制标题
从蓝斑到背侧海马的多巴胺释放促进空间学习和记忆
DOI：
10.1073/pnas.1616515114
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发表时间：
2016-12-20
影响因子：
11.1
通讯作者：
Kandel, Eric R.
中科院分区：
文献类型：
--
作者：
Kempadoo, Kimberly A.;Mosharov, Eugene V.;Kandel, Eric R.
背侧海马体中的多巴胺神经传递对于从空间学习和突触可塑性到潜在的精神障碍如注意力缺陷多动障碍的缺陷的一系列功能至关重要。腹侧被盖区（VTA）被认为是背侧海马多巴胺的来源。然而，有一个令人惊讶的缺乏腹侧被盖区多巴胺轴突在背海马，尽管多巴胺受体的密集网络。我们利用光遗传学、生物化学和行为学方法探索了这一明显的悖论，发现背侧海马中的多巴胺能轴突和随后的多巴胺释放起源于蓝斑（LC）的神经元。LC轴突的光刺激产生的多巴胺释放在背侧海马的增加所揭示的高效液相色谱法。此外，光遗传学诱导的多巴胺从LC释放到背侧海马通过多巴胺D1/D5受体增强选择性注意和空间物体识别。这些结果表明，空间学习和记忆是由LC的去甲肾上腺素能神经元在背侧海马中释放多巴胺所激发的。目前的研究结果对于识别能够正确选择注意力以及成功学习和记忆的神经回路至关重要。
Dopamine neurotransmission in the dorsal hippocampus is critical for a range of functions from spatial learning and synaptic plasticity to the deficits underlying psychiatric disorders such as attention-deficit hyperactivity disorder. The ventral tegmental area (VTA) is the presumed source of dopamine in the dorsal hippocampus. However, there is a surprising scarcity of VTA dopamine axons in the dorsal hippocampus despite the dense network of dopamine receptors. We have explored this apparent paradox using optogenetic, biochemical, and behavioral approaches and found that dopaminergic axons and subsequent dopamine release in the dorsal hippocampus originate from neurons of the locus coeruleus (LC). Photostimulation of LC axons produced an increase in dopamine release in the dorsal hippocampus as revealed by high-performance liquid chromatography. Furthermore, optogenetically induced release of dopamine from the LC into the dorsal hippocampus enhanced selective attention and spatial object recognition via the dopamine D1/D5 receptor. These results suggest that spatial learning and memory are energized by the release of dopamine in the dorsal hippocampus from noradrenergic neurons of the LC. The present findings are critical for identifying the neural circuits that enable proper attention selection and successful learning and memory.