Abstract：
Muscarinic neurotransmission is fundamentally involved in supporting several brain functions by modulating flow of information in brain neural circuits including the hippocampus which displays a remarkable functional segregation along its longitudinal axis. However, how muscarinic neuromodulation contributes to the functional segregation along the hippocampus remains unclear. In this study we show that the nonselective muscarinic receptor agonist carbachol similarly suppresses basal synaptic transmission in the dorsal and ventral CA1 hippocampal field, in a concentration-depended manner. Furthermore, using a ten-pulse stimulation train of varying frequency we found that carbachol changes the frequency filtering properties more in ventral than dorsal hippocampus by facilitating synaptic inputs at a wide range of input frequencies in the ventral compared with dorsal hippocampus. Using the M2 receptor antagonist gallamine and the M4 receptor antagonist tropicamide, we found that M2 receptors are involved in controlling basal synaptic transmission and short-term synaptic plasticity (STSP) in the ventral but not the dorsal hippocampus, while M4 receptors participate in modulating basal synaptic transmission and STSP in both segments of the hippocampus. These results were corroborated by the higher protein expression levels of M2 receptors in the ventral compared with dorsal hippocampus. We conclude that muscarinic transmission modulates excitatory synaptic transmission and short-term synaptic plasticity along the entire rat hippocampus by acting through M4 receptors and recruiting M2 receptors only in the ventral hippocampus. Furthermore, M4 receptors appear to exert a permissive role on the actions of M2 receptors on STSP in the ventral hippocampus. This dorsoventral differentiation of muscarinic modulation is expected to have important implications in information processing along the endogenous hippocampal circuitry.
摘要：
毒蕈碱神经传递通过调节包括海马在内的脑神经回路中的信息流从根本上参与支持多种脑功能，海马沿其纵轴显示出明显的功能隔离。然而,毒蕈碱神经调节如何促进海马的功能分离仍不清楚.在这项研究中，我们表明非选择性毒蕈碱受体激动剂卡巴胆碱类似地抑制背侧和腹侧CA1海马区的基础突触传递，以浓度依赖的方式。此外，使用可变频率的十脉冲刺激序列，我们发现卡巴胆碱通过促进与背侧海马相比在腹侧较宽的输入频率范围内的突触输入，在腹侧比背侧海马中更多地改变了频率滤波特性。使用M2受体拮抗剂没食子胺和M4受体拮抗剂托吡卡胺，我们发现，M2受体参与控制基底突触传递和短期突触可塑性（STSP）在腹侧而不是背侧海马，而M4受体参与调节海马两段的基础突触传递和STSP。与背侧海马相比，腹侧M2受体的蛋白质表达水平更高，证实了这些结果。我们得出的结论是，毒蕈碱传递通过M4受体作用并仅在腹侧海马中募集M2受体，从而调节整个大鼠海马的兴奋性突触传递和短期突触可塑性。此外，M4受体似乎对腹侧海马中M2受体对STSP的作用起允许作用。预计毒蕈碱调节的背腹分化在内源性海马电路的信息处理中具有重要意义。
