Genes and Dynamics of Memory Systems, Neurobiology Unit, Ecole Supérieure de Physique et Chimie Industrielle, CNRS, 10 rue Vauquelin, 75005 Paris, France.
Neuron. 2010 Feb 25;65(4):516-29. doi: 10.1016/j.neuron.2010.01.014.
The dynamics of PKA activity in the olfactory learning and memory center, the mushroom bodies (MBs), are still poorly understood. We addressed this issue in vivo using a PKA FRET probe. Application of dopamine, the main neuromodulator involved in aversive learning, resulted in PKA activation specifically in the vertical lobe, whereas octopamine, involved in appetitive learning, stimulated PKA in all MB lobes. Strikingly, MB lobes were homogeneously activated by dopamine in the learning mutant dunce, showing that Dunce phosphodiesterase plays a major role in the spatial regulation of cAMP dynamics. Furthermore, costimulation with acetylcholine and either dopamine or octopamine led to a synergistic activation of PKA in the MBs that depends on Rutabaga adenylyl cyclase. Our results suggest that Rutabaga acts as a coincidence detector and demonstrate the existence of subcellular domains of PKA activity that could underlie the functional specialization of MB lobes in aversive and appetitive learning.
PKA 活性在嗅觉学习和记忆中心（蘑菇体）中的动态仍知之甚少。我们使用 PKA FRET 探针在体内解决了这个问题。多巴胺的应用，涉及厌恶学习的主要神经调节剂，导致 PKA 特异性激活垂直叶，而章鱼胺，涉及食欲学习，刺激所有 MB 叶的 PKA。引人注目的是，学习突变体傻瓜中的多巴胺均匀激活 MB 叶，表明傻瓜磷酸二酯酶在 cAMP 动力学的空间调节中起主要作用。此外，乙酰胆碱与多巴胺或章鱼胺的共同刺激导致 MB 中 PKA 的协同激活，这依赖于 Rutabaga 腺苷酸环化酶。我们的结果表明 Rutabaga 作为一个巧合探测器，并证明 PKA 活性的亚细胞域的存在，这可能是 MB 叶在厌恶和食欲学习中的功能特化的基础。
