Centre for Studies in Behavioural Neurobiology, Department of Psychology, Concordia University, Montréal, Québec, Canada H4B 1R6.
Neuroscience. 2013 Jan 29;230:72-85. doi: 10.1016/j.neuroscience.2012.11.026. Epub 2012 Nov 29.
The parasubiculum sends its single major output to layer II of the entorhinal cortex, and it may therefore interact with inputs to the entorhinal cortex from other cortical areas, and help to shape the activity of layer II entorhinal cells that project to the hippocampal formation. Cholinergic inputs are thought to contribute to the generation of theta- and gamma-frequency activities in the parasubiculum and entorhinal cortex, and the present study assessed how cholinergic receptor activation affects synaptic responses of the entorhinal cortex to theta- and gamma-frequency stimulation. Depth profiles of field excitatory postsynaptic potentials (fEPSPs) in acute brain slices showed a short-latency negative fEPSP in layer II, consistent with the activation of excitatory synaptic inputs to layer II. Application of the cholinergic agonist carbachol (CCh) suppressed synaptic responses and enhanced paired-pulse facilitation. CCh also resulted in a marked relative facilitation of synaptic responses evoked during short 5-pulse trains of stimulation at both theta- and gamma-frequencies. Application of the M(1) antagonist pirenzepine, but not the M(2) antagonist methoctramine, blocked the facilitation of responses. Inhibition of the M-current or block of GABA(B) receptors had no effect, but the facilitation effect was partially blocked by the N-methyl-d-aspartate (NMDA) antagonist APV, indicating that NMDA receptors play a role. Application of ZD7288, a selective inhibitor of the hyperpolarization-activated cationic current I(h), almost completely blocked the relative facilitation of responses, and the less potent I(h)-blocker Cs(+) also resulted in a partial block. The relative facilitation of synaptic responses induced by CCh is therefore likely mediated by multiple mechanisms including the cholinergic suppression of transmitter release that enhances transmitter availability during repetitive stimulation, NMDA receptor-mediated effects on pre- or postsynaptic function, and cholinergic modulation of the current I(h). These mechanisms likely contribute to the maintenance of effective synaptic communication within parasubicular inputs to the entorhinal cortex during cholinergically induced rhythmic states.
副穹窿将其唯一的主要输出发送到内嗅皮层的 II 层，因此它可能与来自其他皮质区域的内嗅皮层输入相互作用，并帮助塑造投射到海马结构的 II 层内嗅细胞的活动。胆碱能输入被认为有助于副穹窿和内嗅皮层中θ和γ频率活动的产生，本研究评估了胆碱能受体激活如何影响内嗅皮层对θ和γ频率刺激的突触反应。急性脑切片中的场兴奋性突触后电位 (fEPSP) 深度分布显示 II 层中存在潜伏期短的负 fEPSP，与 II 层兴奋性突触输入的激活一致。应用胆碱能激动剂 carbachol (CCh) 可抑制突触反应并增强成对脉冲易化。CCh 还导致在θ和γ频率的短 5 脉冲刺激串期间诱发的突触反应明显相对易化。应用 M1 拮抗剂 pirenzepine，但不是 M2 拮抗剂 methoctramine，可阻断反应的易化。抑制 M 电流或阻断 GABA(B)受体没有影响，但 NMDA 拮抗剂 APV 部分阻断了易化作用，表明 NMDA 受体起作用。应用 ZD7288，一种超极化激活阳离子电流 I(h)的选择性抑制剂，几乎完全阻断了反应的相对易化，较弱的 I(h)阻断剂 Cs(+)也导致部分阻断。因此，CCh 诱导的突触反应的相对易化可能通过多种机制介导，包括胆碱能抑制递质释放，增强重复刺激期间递质的可用性，NMDA 受体对突触前或突触后功能的影响，以及胆碱能调制电流 I(h)。这些机制可能有助于在胆碱能诱导的节律状态下维持副穹窿对内嗅皮层输入的有效突触通讯。
