Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montréal, QC, Canada H4B 1R6.
Neuroscience. 2012 Jan 10;201:1-11. doi: 10.1016/j.neuroscience.2011.11.039. Epub 2011 Nov 28.
Layer II of the parasubiculum (PaS) receives excitatory synaptic input from the CA1 region of the hippocampus and sends a major output to layer II of the medial and lateral entorhinal cortex. The PaS also receives heavy cholinergic innervation from the medial septum, which contributes to the generation of theta-frequency (4-12 Hz) electroencephalographic (EEG) activity. Cholinergic receptor activation exerts a wide range of effects in other areas of the hippocampal formation, including membrane depolarization, changes in neuronal excitability, and suppression of excitatory synaptic responses. The present study was aimed at determining how cholinergic receptor activation modulates excitatory synaptic input to the layer II/III neurons of the PaS in acute brain slices. Field excitatory postsynaptic potentials (fEPSPs) in layer II/III of the PaS were evoked by stimulation of either layer I afferents, or ascending inputs from layer V. Bath-application of the cholinergic agonist carbachol (0.5-10 μM) suppressed the amplitude of fEPSPs evoked by both superficial- and deep layer stimulation, and also enhanced paired-pulse facilitation. Constant bath-application of the GABA(A) antagonist bicuculline (10 μM) failed to eliminate the suppression, indicating that the cholinergic suppression of fEPSPs is not due to increased inhibitory tone. The muscarinic receptor antagonist atropine (1 μM) blocked the suppression of fEPSPs, and the selective M(1)-preferring receptor antagonist pirenzepine (1 μM), but not the M(2)-preferring antagonist methoctramine (1-5 μM), also significantly attenuated the suppression. Therefore, cholinergic receptor activation suppresses excitatory synaptic input to layer II/III neurons of the PaS, and this suppression is mediated in part by M(1) receptor activation.
副穹窿体（PaS）的 II 层接收来自海马 CA1 区的兴奋性突触输入，并将主要输出发送到内侧和外侧内嗅皮层的 II 层。PaS 还从内侧隔核接收大量的胆碱能神经支配，这有助于产生 theta 频率（4-12 Hz）的脑电图（EEG）活动。胆碱能受体激活在海马结构的其他区域产生广泛的影响，包括膜去极化、神经元兴奋性变化和抑制兴奋性突触反应。本研究旨在确定胆碱能受体激活如何调节急性脑切片中 PaS 的 II/III 层神经元的兴奋性突触输入。通过刺激 I 层传入纤维或 V 层的上行输入，在 PaS 的 II/III 层中诱发场兴奋性突触后电位（fEPSP）。用胆碱能激动剂 carbachol（0.5-10 μM）浴应用抑制了浅层和深层刺激诱发的 fEPSP 的幅度，并增强了成对脉冲易化。持续的 GABA(A) 拮抗剂荷包牡丹碱（10 μM）的浴应用未能消除抑制，表明胆碱能对 fEPSP 的抑制不是由于抑制性张力增加所致。毒蕈碱受体拮抗剂阿托品（1 μM）阻断了 fEPSP 的抑制，而选择性 M(1) 受体偏好拮抗剂 pirenzepine（1 μM），而不是 M(2) 受体偏好拮抗剂 methoctramine（1-5 μM），也显著减弱了抑制。因此，胆碱能受体激活抑制 PaS 的 II/III 层神经元的兴奋性突触输入，这种抑制部分是通过 M(1) 受体激活介导的。
