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星形细胞介导腹侧被盖区多巴胺神经元的持续突触调节
作者:小柯机器人 发布时间:2022/11/20 20:42:25


意大利帕多瓦大学Giorgio Carmignoto和Marta Gómez-Gonzalo共同合作,近期取得重要工作进展。他们研究发现星形细胞介导腹侧被盖区(VTA)多巴胺神经元的持续性突触调节。相关研究工作2022年11月17日在线发表于《自然—神经科学》杂志上。

研究人员描述了小鼠VTA中长期突触可塑性的一种迄今尚未确定的机制。他们发现,单个多巴胺神经元的爆发性放电诱导相邻多巴胺神经元上兴奋性突触的持久增强,这主要取决于星形胶质细胞中Ca2+的升高,由共同定位于同一星形胶质细胞过程的内源性大麻素CB1和多巴胺D2受体介导,以及突触前代谢型谷氨酸受体的激活。与这些发现一致,星形胶质细胞的选择性体内激活增加了VTA中多巴胺神经元的爆发性放电,并诱导运动过度活跃。因此,星形胶质细胞在调节VTA多巴胺神经元功能活动中起着关键作用。

据介绍,腹侧被盖区(VTA)谷氨酸能传递的可塑性是调节靶区多巴胺神经元爆发放电和阶段性多巴胺释放的基本机制。这些过程编码基本的行为反应,包括运动活动、学习和激励行为。

附:英文原文

Title: Astrocytes mediate long-lasting synaptic regulation of ventral tegmental area dopamine neurons

Author: Requie, Linda Maria, Gmez-Gonzalo, Marta, Speggiorin, Michele, Manag, Francesca, Melone, Marcello, Congiu, Mauro, Chiavegato, Angela, Lia, Annamaria, Zonta, Micaela, Losi, Gabriele, Henriques, Vanessa Jorge, Pugliese, Arianna, Pacinelli, Giada, Marsicano, Giovanni, Papaleo, Francesco, Muntoni, Anna Lisa, Conti, Fiorenzo, Carmignoto, Giorgio

Issue&Volume: 2022-11-17

Abstract: The plasticity of glutamatergic transmission in the ventral tegmental area (VTA) represents a fundamental mechanism in the modulation of dopamine neuron burst firing and phasic dopamine release at target regions. These processes encode basic behavioral responses, including locomotor activity, learning and motivated behaviors. Here we describe a hitherto unidentified mechanism of long-term synaptic plasticity in mouse VTA. We found that the burst firing in individual dopamine neurons induces a long-lasting potentiation of excitatory synapses on adjacent dopamine neurons that crucially depends on Ca2+ elevations in astrocytes, mediated by endocannabinoid CB1 and dopamine D2 receptors co-localized at the same astrocytic process, and activation of pre-synaptic metabotropic glutamate receptors. Consistent with these findings, selective in vivo activation of astrocytes increases the burst firing of dopamine neurons in the VTA and induces locomotor hyperactivity. Astrocytes play, therefore, a key role in the modulation of VTA dopamine neuron functional activity.

DOI: 10.1038/s41593-022-01193-4

Source: https://www.nature.com/articles/s41593-022-01193-4

期刊信息

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:21.126
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex