Inhibitory Pedunculopontine Neurons Gate Dopamine-Mediated Motor Actions of Unsigned Valence.

IF 4.8 2区 医学 Q1 NEUROSCIENCES
Sirin Zhang, Juan Mena-Segovia, Nadine K Gut
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引用次数: 0

Abstract

Background: The pedunculopontine nucleus (PPN) maintains a bidirectional connectivity with the basal ganglia that supports their shared roles in the selection and execution of motor actions. Previous studies identified a role for PPN neurons in goal-directed behavior, but the cellular substrates underlying this function have not been elucidated. We recently revealed the existence of a monosynaptic GABAergic input from the PPN that inhibits dopamine neurons of the substantia nigra. Activation of this pathway interferes with the execution of learned motor sequences when the actions are rewarded, even though the inhibition of dopamine neurons did not shift the value of the action, hence suggesting executive control over the gating of behavior.

Objective: To test the attributes of the inhibition of dopamine neurons by the PPN in the context of goal-directed behavior regardless of whether the outcome is positively or negatively reinforced.

Methods: We delivered optogenetic stimulation to PPN GABAergic axon terminals in the substantia nigra during a battery of behavioral tasks with positive and negative valence.

Results: Inhibition of dopamine neurons by PPN optogenetic activation during an appetitive task impaired the initiation and overall execution of the behavioral sequence without affecting the consumption of reward. During an active avoidance task, the same activation impaired the ability of mice to avoid a foot shock, but their escape response was unaffected. In addition, responses to potential threats were significantly attenuated.

Conclusion: Our results show that PPN GABAergic neurons modulate learned, goal-directed behavior of unsigned valence without affecting overall motor behavior.

抑制性脊髓神经元对多巴胺介导的无符号价值运动行为进行把关
背景:足底神经核(PPN)与基底神经节保持双向联系,支持它们在选择和执行运动动作中的共同作用。以前的研究发现了 PPN 神经元在目标定向行为中的作用,但这一功能的细胞基础尚未阐明。最近,我们发现了一种来自 PPN 的单突触 GABA 能输入,它能抑制黑质的多巴胺神经元。当动作得到奖励时,激活这条通路会干扰已学会的动作序列的执行,即使多巴胺神经元的抑制并没有改变动作的价值,因此表明了对行为门控的执行控制:目的:测试多巴胺神经元在目标定向行为中的抑制属性,无论结果是积极还是消极:方法:在一系列具有积极和消极价值的行为任务中,我们对黑质中的PPN GABA能轴突末端进行光遗传刺激:结果:在执行食欲任务时,PPN光遗传激活对多巴胺神经元的抑制损害了行为序列的启动和整体执行,但不影响奖赏的消耗。在主动回避任务中,同样的激活损害了小鼠回避脚震的能力,但它们的逃跑反应不受影响。此外,小鼠对潜在威胁的反应也明显减弱:我们的研究结果表明,PPN GABAergic神经元可调节未符号valence的习得性目标定向行为,而不会影响整体运动行为。
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来源期刊
Current Neuropharmacology
Current Neuropharmacology 医学-神经科学
CiteScore
8.70
自引率
1.90%
发文量
369
审稿时长
>12 weeks
期刊介绍: Current Neuropharmacology aims to provide current, comprehensive/mini reviews and guest edited issues of all areas of neuropharmacology and related matters of neuroscience. The reviews cover the fields of molecular, cellular, and systems/behavioural aspects of neuropharmacology and neuroscience. The journal serves as a comprehensive, multidisciplinary expert forum for neuropharmacologists and neuroscientists.
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