Sunkavalli Praneel S, Madara Joseph C, Christenson Lauren F, Diaz Adriana, Chen Janelle, Ravotto Luca, Patriarchi Tommaso, Andermann Mark L, Zhang Stephen X
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
bioRxiv. 2025 Jun 2:2025.05.29.656898. doi: 10.1101/2025.05.29.656898.
The rise and fall of motivational states may take place over timescales as long as many days. We used mouse mating behavior to model how the brain orchestrates slow-timescale changes in motivation. Male mice become sexually satiated after successful matings, and their motivation to mate gradually recovers over a week. Using deep-brain fluorescence-lifetime imaging in the medial preoptic area (MPOA), we found that tonic dopamine transmission-which regulates mating drive-also declined after mating and re-emerged over a week. Two mechanisms regulated dopamine transmission. First, successful mating transiently reduced tonic firing of hypothalamic dopamine-releasing neurons, thereby inhibiting dopamine release and mating behavior. Second, mating reduced the ability of these neurons to produce and release dopamine, and this ability gradually returned over the week-long recovery time course. Therefore, fast and slow mechanisms of neuronal plasticity cooperate to control the early and late phases of motivational dynamics, respectively.
动机状态的起伏可能发生在长达数天的时间尺度上。我们利用小鼠的交配行为来模拟大脑如何协调动机的缓慢时间尺度变化。雄性小鼠在成功交配后会出现性满足，它们的交配动机在一周内逐渐恢复。通过在内侧视前区（MPOA）进行深部脑荧光寿命成像，我们发现调节交配驱动力的持续性多巴胺传递在交配后也会下降，并在一周后重新出现。有两种机制调节多巴胺传递。首先，成功交配会短暂降低下丘脑多巴胺释放神经元的紧张性放电，从而抑制多巴胺释放和交配行为。其次，交配降低了这些神经元产生和释放多巴胺的能力，而这种能力在长达一周的恢复过程中逐渐恢复。因此，神经元可塑性的快速和缓慢机制分别协同控制动机动态的早期和晚期阶段。
