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腹侧苍白球γ-氨基丁酸(GABA)和谷氨酸能神经元通过对腹侧被盖区(VTA)不同细胞类型的独特调节来驱动趋近和回避行为。

Ventral pallidum GABA and glutamate neurons drive approach and avoidance through distinct modulation of VTA cell types.

作者信息

Faget Lauren, Oriol Lucie, Lee Wen-Chun, Sargent Cody, Ramanathan Dhakshin, Hnasko Thomas S

机构信息

Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA.

Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA.

出版信息

bioRxiv. 2023 Jul 12:2023.07.12.548750. doi: 10.1101/2023.07.12.548750.

Abstract

The ventral pallidum (VP) contains GABA and glutamate (Glut) neurons projecting to ventral tegmental area (VTA) whose stimulation drives approach and avoidance, respectively. Yet little is known about the cell-type-specific mechanisms by which VP projections to VTA drive behavior. Here, we found that both VP GABA and Glut neurons were activated during approach to reward or delivery of an aversive stimulus. Stimulation of VP GABA neurons inhibited VTA GABA, but activated dopamine (DA) and glutamate neurons. Remarkably, this cell-type-specific recruitment was behavior-contingent such that VTA recruitment was inhibited when evoked by the subject's own action. Conversely, VP Glut neurons activated VTA GABA, as well as DA and Glut neurons, despite driving aversion. However, VP Glut neurons evoked DA in reward-associated ventromedial nucleus accumbens (NAc), but reduced DA in aversion-associated dorsomedial NAc. These findings show how heterogeneous VP cell types can engage VTA cell types to shape approach and avoidance behaviors.

摘要

腹侧苍白球(VP)包含向腹侧被盖区(VTA)投射的γ-氨基丁酸(GABA)能和谷氨酸(Glut)能神经元,分别刺激它们会驱动趋近和回避行为。然而,关于VP向VTA的投射驱动行为的细胞类型特异性机制,我们知之甚少。在这里,我们发现,在趋近奖励或给予厌恶刺激的过程中,VP的GABA能和Glut能神经元均被激活。刺激VP的GABA能神经元会抑制VTA的GABA能神经元,但会激活多巴胺(DA)能和谷氨酸能神经元。值得注意的是,这种细胞类型特异性的募集是行为依赖的,即当由受试者自身的行为诱发时,VTA的募集会受到抑制。相反,VP的Glut能神经元尽管驱动回避行为,但会激活VTA的GABA能神经元以及DA能和Glut能神经元。然而,VP的Glut能神经元在与奖励相关的伏隔核腹内侧核(NAc)中诱发DA释放,但在与厌恶相关的伏隔核背内侧核中减少DA释放。这些发现表明,VP中不同的细胞类型如何与VTA中的细胞类型相互作用,从而塑造趋近和回避行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234e/10369949/eea80f17e74a/nihpp-2023.07.12.548750v1-f0001.jpg

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