Role of Dopamine Neurons in Familiarity.
Role of Dopamine Neurons in Familiarity.
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多巴胺神经元在熟悉度中的作用。
DOI：
10.1101/2023.10.25.564006
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Mingote,Susana
中科院分区：
文献类型：
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作者：
Fleury,Sixtine;Kolaric,Rhonda;Espera,Justin;Ha,Quan;Tomaio,Jacquelyn;Gether,Ulrik;Sørensen,AndreasToft;Mingote,Susana
多巴胺神经元发出环境刺激突显的信号并影响学习，尽管这些神经元是否也决定了记忆的突显还不太清楚。腹侧被盖区(VTA)多巴胺神经元在新物体存在时增加其放电，而在反复、无关紧要的暴露时减少其放电，标志着从新奇到熟悉的转变。这项研究调查了在随后的新物体识别(NOR)测试中，重复暴露熟悉的物体时，多巴胺神经元的活动如何影响动物对新物体的偏好。我们假设，单一的熟悉课程不足以降低多巴胺的活性，从而使对熟悉物体的记忆保持突出，导致对熟悉和新物体的平等探索，并导致较弱的NOR辨别。相比之下，多次熟悉课程可能会更有效地抑制多巴胺活动，降低熟悉对象的显着性，并增强随后的新鲜感辨别能力。我们在小鼠身上的实验表明，与单一的熟悉会议相比，多个熟悉会议减少了VTA多巴胺神经元的激活(通过c-Fos表达来衡量)，并增强了对新奇事物的辨别能力。对新奇事物有反应的多巴胺神经元主要位于VTA的黑质旁核，表达囊泡型谷氨酸转运体2转录本，标记为多巴胺-谷氨酸神经元。单次治疗期间对多巴胺神经元的化学生成抑制作用与多次治疗的效果相当，从而改善了NOR。这些发现表明，在从新奇到熟悉的转变过程中，多巴胺神经元的一个关键作用是调节对象记忆的突出性。
Dopamine neurons signal the salience ofenvironmentalstimuli and influence learning, although it is less clear if these neurons also determine the salience of memories. Ventral tegmental area (VTA) dopamine neurons increase their firing in the presence of new objects and reduce it upon repeated, inconsequential exposures, marking the shift from novelty to familiarity. This study investigates how dopamine neuron activity during repeated familiar object exposure affects an animal's preference for new objects in a subsequent novel object recognition (NOR) test. We hypothesize that a single familiarization session will not sufficiently lower dopamine activity, such that the memory of a familiar object remains salient, leading to equal exploration of familiar and novel objects and weaker NOR discrimination. In contrast, multiple familiarization sessions likely suppress dopamine activity more effectively, reducing the salience of the familiar object and enhancing subsequent novelty discrimination. Our experiments in mice indicated that multiple familiarization sessions reduce VTA dopamine neuron activation, as measured by c‐Fos expression, and enhance novelty discrimination compared with a single familiarization session. Dopamine neurons that show responsiveness to novelty were primarily located in the paranigral nucleus of the VTA and expressed vesicular glutamate transporter 2 transcripts, marking them as dopamine–glutamate neurons. Chemogenetic inhibition of dopamine neurons during a single session paralleled the effects of multiple sessions, improving NOR. These findings suggest that a critical role of dopamine neurons during the transition from novelty to familiarity is to modulate the salience of an object's memory.