背景:足肌桥核(PPN)与基底神经节保持双向连接,支持它们在运动动作的选择和执行中的共同作用。先前的研究确定了PPN神经元在目标导向行为中的作用,但这种功能背后的细胞底物尚未阐明。我们最近揭示了来自PPN的单突触GABA能输入的存在,该输入抑制了黑质的多巴胺神经元。当行动得到奖励时,该途径的激活会干扰学习的运动序列的执行,即使多巴胺神经元的抑制并没有改变作用的价值,因此建议对行为门控的执行控制。
目的:在目标导向行为的背景下,无论结果是积极还是消极,测试PPN对多巴胺神经元的抑制属性。
方法:我们在一系列具有正价和负价的行为任务中向黑质中的PPNGABA能轴突末端传递了光遗传学刺激。
结果:食欲任务期间PPN光遗传学激活对多巴胺神经元的抑制会损害行为序列的启动和整体执行,而不会影响奖励的消耗。在主动回避任务期间,同样的激活损害了小鼠避免脚部电击的能力,但是他们的逃生反应没有受到影响。此外,对潜在威胁的反应显著减弱.
结论:我们的结果表明PPNGABA能神经元调节学习,无符号价的目标导向行为,而不影响整体运动行为。
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.
CONCLUSIONS: Our results show that PPN GABAergic neurons modulate learned, goal-directed behavior of unsigned valence without affecting overall motor behavior.