Optogenetic manipulations have transformed neuroscience in recent years. While sophisticated tools now exist for controlling the firing patterns of neurons, it remains challenging to optogenetically define the plasticity state of individual synapses. A variety of synapses in the mammalian brain express presynaptic long‐term potentiation (LTP) upon elevation of presynaptic cyclic adenosine monophosphate (cAMP), but the molecular expression mechanisms as well as the impact of presynaptic LTP on network activity and behavior are not fully understood. In order to establish optogenetic control of presynaptic cAMP levels and thereby presynaptic potentiation, we developed synaptoPAC, a presynaptically targeted version of the photoactivated adenylyl cyclase bPAC. In cultures of hippocampal granule cells of Wistar rats, activation of synaptoPAC with blue light increased action potential‐evoked transmission, an effect not seen in hippocampal cultures of non‐granule cells. In acute brain slices of C57BL/6N mice, synaptoPAC activation immediately triggered a strong presynaptic potentiation at mossy fiber synapses in CA3, but not at Schaffer collateral synapses in CA1. Following light‐triggered potentiation, mossy fiber transmission decreased within 20 min, but remained enhanced still after 30 min. The optogenetic potentiation altered the short‐term plasticity dynamics of release, reminiscent of presynaptic LTP. Our work establishes synaptoPAC as an optogenetic tool that enables acute light‐controlled potentiation of transmitter release at specific synapses in the brain, facilitating studies of the role of presynaptic potentiation in network function and animal behavior in an unprecedented manner.

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SynaptoPAC，一种用于诱导突触前可塑性的光遗传学工具

近年来，光遗传学操纵已经改变了神经科学。虽然现在存在用于控制神经元放电模式的复杂工具，但光遗传定义单个突触的可塑性状态仍然具有挑战性。突触前环状单磷酸腺苷（cAMP）升高后，哺乳动物脑中的各种突触会表达突触前长期增强（LTP），但尚未充分了解突触前LTP对网络活动和行为的影响以及分子表达机制。 。为了建立突触前cAMP水平的光遗传学控制，从而突触前增强，我们开发了synaptoPAC，这是光活化腺苷酸环化酶bPAC的突触前靶向版本。在Wistar大鼠的海马颗粒细胞培养物中，蓝光激活synaptoPAC会增加动作电位诱发的传递，这在非颗粒细胞的海马培养物中未见过。在C57BL / 6N小鼠的急性脑切片中，synaptoPAC活化立即在CA3的苔藓纤维突触处触发了强烈的突触前增强作用，但在CA1的Schaffer侧突触处却未触发。光触发增强后，苔藓纤维的传输在20分钟内下降，但在30分钟后仍保持增强。光遗传学增强改变了释放的短期可塑性动力学，让人联想到突触前LTP。我们的工作将synaptoPAC确立为一种光遗传学工具，可以在大脑中特定的突触处实现对光发射器的急性光控增强，