Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ, USA.
Curr Neuropharmacol. 2024;22(9):1540-1550. doi: 10.2174/1570159X21666230911103520.
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.
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.
We delivered optogenetic stimulation to PPN GABAergic axon terminals in the substantia nigra during a battery of behavioral tasks with positive and negative valence.
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.
Our results show that PPN GABAergic neurons modulate learned, goal-directed behavior of unsigned valence without affecting overall motor behavior.
被盖核（PPN）与基底神经节之间存在双向连接，支持它们在运动动作的选择和执行中发挥共同作用。先前的研究确定了 PPN 神经元在目标导向行为中的作用，但这一功能的细胞基础尚未阐明。我们最近发现了来自 PPN 的单突触 GABA 能传入，它抑制黑质中的多巴胺神经元。当动作得到奖励时，激活这条通路会干扰习得的运动序列的执行，即使多巴胺神经元的抑制并没有改变动作的价值，因此这表明对行为的门控具有执行控制作用。
无论结果是正强化还是负强化，测试 PPN 对多巴胺神经元的抑制在目标导向行为中的作用。
我们在一系列具有正性和负性效价的行为任务中，对黑质中 PPN GABA 能轴突末梢进行光遗传学刺激。
在一个奖赏性任务中，PPN 光遗传学激活抑制多巴胺神经元，而不影响奖赏的消耗，从而损害了行为序列的启动和整体执行。在主动回避任务中，同样的激活会损害小鼠避免足部电击的能力，但它们的逃避反应不受影响。此外，对潜在威胁的反应明显减弱。
我们的结果表明，PPN GABA 能神经元调节无符号效价的习得性、目标导向行为，而不影响整体运动行为。
