Cyclic AMP-dependent plasticity underlies rapid changes in odor coding associated with reward learning.
Cyclic AMP-dependent plasticity underlies rapid changes in odor coding associated with reward learning.
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环 AMP 依赖性可塑性是与奖励学习相关的气味编码快速变化的基础。
DOI：
10.1073/pnas.1709037115
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发表时间：
2018
影响因子：
11.1
通讯作者：
Tomchik,SethM
中科院分区：
文献类型：
--
作者：
Louis,Thierry;Stahl,Aaron;Boto,Tamara;Tomchik,SethM
学习和记忆依赖于多巴胺和下游cAMP依赖的可塑性在不同的生物体。尽管cAMP信号传导的中心作用，但尚不清楚cAMP依赖性可塑性如何驱动编码记忆痕迹或痕迹的神经元生理学的连贯变化。果蝇的蘑菇体（mushroom body，MB）在嗅觉经典条件反射中起着重要作用，cAMP信号分子是MB神经元正常记忆所必需的。为了评估cAMP依赖的可塑性在学习中的作用，我们研究了cAMP操作和嗅觉经典条件反射如何调节MB的嗅觉反应与体内成像。升高cAMP水平或光遗传学产生MB神经元的可塑性，改变它们对气味的反应。气味诱发的Ca 2+反应显示净促进整个解剖区域。在单细胞水平上，神经元表现出对cAMP升高的异质性反应，表明cAMP驱动MB神经元离散子集的可塑性。嗅觉食欲调节增强MB气味反应，模仿cAMP依赖的可塑性的方向性和幅度。将cAMP升高到与食欲调节相当的水平也产生了可塑性，这表明调节过程中产生的cAMP影响MB中的气味诱发反应。最后，我们发现，这种可塑性是依赖于芜菁I型腺苷酸环化酶，连接cAMP依赖的可塑性的行为修改。总的来说，这些数据表明，学习产生强大的cAMP依赖性可塑性内在MB神经元，这是偏向自然奖励学习。这表明，cAMP信号可能有助于调节内在MB对显着刺激的反应。
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. InDrosophila, 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 Ca2+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.