Abstract：
Dopamine critically influences reward processing, sensory perception, and motor control. Yet, the modulation of dopaminergic signaling by sensory experiences is not fully delineated. Here, by manipulating sensory experience using bilateral single-row whisker deprivation, we demonstrated that gene transcription in the dopaminergic signaling pathway (DSP) undergoes experience-dependent plasticity in both granular and supragranular layers of the primary somatosensory (barrel) cortex (S1). Sensory experience and deprivation compete for the regulation of DSP transcription across neighboring cortical columns, and sensory deprivation-induced changes in DSP are topographically constrained. These changes in DSP extend beyond cortical map plasticity and influence neuronal information processing. Pharmacological regulation of D2 receptors, a key component of DSP, revealed that D2 receptor activation suppresses excitatory neuronal excitability, hyperpolarizes the action potential threshold, and reduces the instantaneous firing rate. These findings suggest that the dopaminergic drive originating from midbrain dopaminergic neurons, targeting the sensory cortex, is subject to experience-dependent regulation and might create a regulatory feedback loop for modulating sensory processing. Finally, using topological gene network analysis and mutual information, we identify the molecular hubs of experience-dependent plasticity of DSP. These findings provide new insights into the mechanisms by which sensory experience shapes dopaminergic signaling in the brain and might help unravel the sensory deficits observed after dopamine depletion.
摘要：
多巴胺严重影响奖励处理，感官知觉，和电机控制。然而，感觉经验对多巴胺能信号的调节还没有完全描述。这里,通过使用双侧单行晶须剥夺进行人工感官体验，我们证明，多巴胺能信号通路（DSP）中的基因转录在初级体感（桶状）皮层（S1）的颗粒层和球上层都经历了经验依赖性可塑性。感官体验和剥夺竞争DSP转录在邻近皮质柱中的重新调节，感觉剥夺引起的DSP变化在地形上受到限制。DSP中的这些变化超出了皮质图的可塑性，并影响神经元信息处理。D2受体的药理学规范，DSP的关键部件,揭示D2受体激活抑制兴奋性神经元兴奋性，超极化-使动作电位阈值，并降低瞬时点火率。这些发现表明，多巴胺能驱动起源于中脑多巴胺能神经元，瞄准感觉皮层，受到经验依赖的调节，可能会创建一个调节反馈回路来调节感官处理。最后,利用拓扑基因网络分析和互信息，我们确定了DSP经验依赖可塑性的分子中心。这些发现为感觉体验塑造大脑中多巴胺能信号的机制提供了新的见解，并可能有助于解开多巴胺耗尽后观察到的感觉缺陷。
