Dysfunctional N-methyl-D-aspartate receptors (NMDARs) and cyclic adenosine monophosphate (cAMP) have been associated with deficits in synaptic plasticity and cognition found in neurodegenerative and neuropsychiatric disorders such as Alzheimer’s disease (AD) and schizophrenia. Therapeutic approaches that indirectly enhance NMDAR function through increases in glycine and/or D-serine levels as well as inhibition of phosphodiesterases that reduces degradation of cAMP, are expected to enhance synaptic strength, connectivity and to potentially impact cognition processes. The present in vivo study investigated effects of subcutaneous administration of D-serine, the glycine transporter 1 (GlyT1) inhibitor SSR504734 and the PDE4 inhibitor rolipram, on network oscillations, connectivity and long-term potentiation (LTP) at the hippocampi circuits in Sprague-Dawley rats. In conscious animals, multichannel EEG recordings assessed network oscillations and connectivity at frontal and hippocampal CA1–CA3 circuits. Under urethane anaesthesia, field excitatory postsynaptic potentials (fEPSPs) were measured in the CA1 subfield of the hippocampus after high-frequency stimulation (HFS) of the Schaffer collateral-CA1 (SC) pathway. SSR504734 and rolipram significantly increased slow theta oscillations (4–6.5 Hz) at the CA1–CA3, slow gamma oscillations (30–50 Hz) in the frontal areas and enhanced coherence in the CA1–CA3 network, which were dissociated from motor behaviour. SSR504734 enhanced short-term potentiation (STP) and fEPSP responses were extended into LTP response, whereas the potentiation of EPSP slope was short-lived to STP with rolipram. Unlike glycine, increased levels of D-serine had no effect on network oscillations and limits the LTP induction and expression. The present data support a facilitating role of glycine and cAMP on network oscillations and synaptic efficacy at the CA3–CA1 circuit in rats, whereas raising endogenous D-serine levels had no such beneficial effects.

功能失调的 N-甲基-D-天冬氨酸受体 (NMDAR) 和环磷酸腺苷 (cAMP) 与神经退行性和神经精神疾病（如阿尔茨海默病 (AD) 和精神分裂症）中发现的突触可塑性和认知缺陷有关。通过增加甘氨酸和/或 D-丝氨酸水平以及抑制减少 cAMP 降解的磷酸二酯酶来间接增强 NMDAR 功能的治疗方法有望增强突触强度、连接性并可能影响认知过程。目前的体内研究调查了皮下给药 D-丝氨酸、甘氨酸转运蛋白 1 (GlyT1) 抑制剂 SSR504734 和 PDE4 抑制剂咯利普兰对网络振荡的影响，Sprague-Dawley 大鼠海马回路的连通性和长时程增强 (LTP)。在有意识的动物中，多通道脑电图记录评估了额叶和海马 CA1-CA3 回路的网络振荡和连通性。在氨基甲酸乙酯麻醉下，高频刺激 (HFS) 的 Schaffer 侧枝-CA1 (SC) 通路后，在海马 CA1 亚区测量场兴奋性突触后电位 (fEPSP)。SSR504734 和咯利普兰显着增加 CA1-CA3 处的慢θ振荡（4-6.5 Hz）、额叶区域的慢伽马振荡（30-50 Hz）和 CA1-CA3 网络的一致性增强，这与运动行为无关。SSR504734 增强的短期增强 (STP) 和 fEPSP 响应扩展为 LTP 响应，而使用咯利普兰对 STP 的 EPSP 斜率增强是短暂的。与甘氨酸不同，D-丝氨酸水平的增加对网络振荡没有影响，并限制了 LTP 的诱导和表达。目前的数据支持甘氨酸和 cAMP 对大鼠 CA3-CA1 回路的网络振荡和突触功效的促进作用，而提高内源性 D-丝氨酸水平没有这种有益作用。