cAMP is a positive regulator tightly involved in certain types of synaptic plasticity and related memory functions. However, its spatiotemporal roles at the synaptic and neural circuit levels remain elusive. Using a combination of a cAMP optogenetics approach and voltage-sensitive dye (VSD) imaging with electrophysiological recording, we define a novel capacity of postsynaptic cAMP in enabling dentate gyrus long-term potentiation (LTP) and depolarization in acutely prepared murine hippocampal slices. To manipulate cAMP levels at medial perforant path to granule neuron (MPP-DG) synapses by light, we generated transgenic (Tg) mice expressing photoactivatable adenylyl cyclase (PAC) in DG granule neurons. Using these Tg(CMV-Camk2a-RFP/bPAC)3Koka mice, we recorded field excitatory postsynaptic potentials (fEPSPs) from MPP-DG synapses and found that photoactivation of PAC during tetanic stimulation enabled synaptic potentiation that persisted for at least 30 min. This form of LTP was induced without the need for GABA receptor blockade that is typically required for inducing DG plasticity. The paired-pulse ratio (PPR) remained unchanged, indicating the cAMP-dependent LTP was likely postsynaptic. By employing fast fluorescent voltage-sensitive dye (VSD: di-4-ANEPPS) and fluorescence imaging, we found that photoactivation of the PAC actuator enhanced the intensity and extent of dentate gyrus depolarization triggered following tetanic stimulation. These results demonstrate that the elevation of cAMP in granule neurons is capable of rapidly enhancing synaptic strength and neuronal depolarization. The powerful actions of cAMP are consistent with this second messenger having a critical role in the regulation of synaptic function.

cAMP是一种正调节剂，与某些类型的突触可塑性和相关的记忆功能密切相关。但是，其在突触和神经回路水平的时空作用仍然难以捉摸。通过将cAMP光遗传学方法和电压敏感染料（VSD）成像与电生理记录相结合，我们定义了突触后cAMP在使齿状回长期增强（LTP）和去极化在急性制备的小鼠海马切片中具有的新能力。若要通过光操纵到颗粒神经元（MPP-DG）突触的内侧穿孔路径上的cAMP水平，我们生成了在DG颗粒神经元中表达光活化腺苷酸环化酶（PAC）的转基因（Tg）小鼠。使用这些Tg（CMV-Camk2a-RFP / bPAC）3Koka小鼠，我们记录了MPP-DG突触的现场兴奋性突触后电位（fEPSP），发现强直性刺激过程中PAC的光活化使突触增强持续了至少30分钟。这种形式的LTP不需要诱导DG可塑性通常需要的GABA受体阻断。配对脉冲比率（PPR）保持不变，表明依赖cAMP的LTP可能在突触后。通过采用快速荧光电压敏感染料（VSD：di-4-ANEPPS）和荧光成像，我们发现PAC致动器的光活化增强了强直刺激后触发的齿状回去极化的强度和程度。这些结果表明，颗粒神经元中cAMP的升高能够迅速增强突触强度和神经元去极化。