Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458.
Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458
Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):E448-E457. doi: 10.1073/pnas.1709037115. Epub 2017 Dec 28.
Learning and memory rely on dopamine and downstream cAMP-dependent plasticity across diverse organisms. Despite the central role of cAMP signaling, it is not known how cAMP-dependent plasticity drives coherent changes in neuronal physiology that encode the memory trace, or engram. In , the mushroom body (MB) is critically involved in olfactory classical conditioning, and cAMP signaling molecules are necessary and sufficient for normal memory in intrinsic MB neurons. To evaluate the role of cAMP-dependent plasticity in learning, we examined how cAMP manipulations and olfactory classical conditioning modulate olfactory responses in the MB with in vivo imaging. Elevating cAMP pharmacologically or optogenetically produced plasticity in MB neurons, altering their responses to odorants. Odor-evoked Ca responses showed net facilitation across anatomical regions. At the single-cell level, neurons exhibited heterogeneous responses to cAMP elevation, suggesting that cAMP drives plasticity to discrete subsets of MB neurons. Olfactory appetitive conditioning enhanced MB odor responses, mimicking the cAMP-dependent plasticity in directionality and magnitude. Elevating cAMP to equivalent levels as appetitive conditioning also produced plasticity, suggesting that the cAMP generated during conditioning affects odor-evoked responses in the MB. Finally, we found that this plasticity was dependent on the Rutabaga type I adenylyl cyclase, linking cAMP-dependent plasticity to behavioral modification. Overall, these data demonstrate that learning produces robust cAMP-dependent plasticity in intrinsic MB neurons, which is biased toward naturalistic reward learning. This suggests that cAMP signaling may serve to modulate intrinsic MB responses toward salient stimuli.
学习和记忆依赖于多巴胺和下游的 cAMP 依赖性可塑性，这在不同的生物体中都有体现。尽管 cAMP 信号发挥着核心作用，但人们尚不清楚 cAMP 依赖性可塑性如何驱动神经元生理学的相干变化，从而对记忆痕迹或记忆库进行编码。在这篇文章中，蘑菇体（MB）在嗅觉经典条件反射中起着至关重要的作用，而 cAMP 信号分子对于内在 MB 神经元的正常记忆是必需且充分的。为了评估 cAMP 依赖性可塑性在学习中的作用，我们通过体内成像技术研究了 cAMP 操作和嗅觉经典条件反射如何调节 MB 中的嗅觉反应。药理学或光遗传学方法升高 cAMP 可使 MB 神经元产生可塑性，改变它们对气味剂的反应。气味诱发的 Ca 反应在整个解剖区域均显示出净促进作用。在单细胞水平上，神经元对 cAMP 升高的反应表现出异质性，这表明 cAMP 驱动可塑性作用于离散的 MB 神经元亚群。嗅觉奖赏性条件反射增强了 MB 的气味反应，在方向和幅度上模拟了 cAMP 依赖性可塑性。将 cAMP 升高到与奖赏性条件反射相当的水平也会产生可塑性，这表明条件反射过程中产生的 cAMP 会影响 MB 中气味诱发的反应。最后，我们发现这种可塑性依赖于 Rutabaga 型 I 腺苷酸环化酶，将 cAMP 依赖性可塑性与行为改变联系起来。总的来说，这些数据表明，学习会在内在的 MB 神经元中产生强大的 cAMP 依赖性可塑性，这种可塑性偏向于自然奖励学习。这表明 cAMP 信号可能有助于调节内在 MB 对显著刺激的反应。
