Hasselmo M E, Schnell E
Department of Psychology, Harvard University, Cambridge, Massachusetts 02138.
J Neurosci. 1994 Jun;14(6):3898-914. doi: 10.1523/JNEUROSCI.14-06-03898.1994.
ACh may set the dynamics of cortical function to those appropriate for learning new information. In models of the putative associative memory function of piriform cortex, selective suppression of intrinsic but not afferent fiber synaptic transmission by ACh prevents recall of previous input from interfering with the learning of new input (Hasselmo, 1993). Selective cholinergic suppression may play a similar role in the hippocampal formation, where Schaffer collateral synapses in stratum radiatum (s. rad) may store associations between activity in region CA3 and the entorhinal cortex input to region CA1 terminating in stratum lacunosum-moleculare (s. l-m). A computational model of region CA1 predicts that for effective associative memory function of the Schaffer collaterals, cholinergic suppression of synaptic transmission should be stronger in s. rad than in s. l-m. In the hippocampal slice preparation, we tested the effect of the cholinergic agonist carbachol (0.01-500 microM) on synaptic transmission in s. rad and s. l-m. Stimulating and recording electrodes were simultaneously placed in both layers, allowing analysis of the effect of carbachol on synaptic potentials in both layers during the same perfusion in each slice. Carbachol produced a significantly stronger suppression of stimulus-evoked EPSPs in s. rad than in s. l-m at all concentrations greater than 1 microM. At 100 microM, EPSP initial slopes were suppressed by 89.1 +/- 3.0% in s. rad, but only by 40.1 +/- 4.1% in s. l-m. The muscarinic antagonist atropine (1 microM) blocked cholinergic suppression in both layers. These data support the hypothesis that synaptic modification of the Schaffer collaterals may store associations between activity in region CA3 and the afferent input to region CA1 from the entorhinal cortex. In simulations, feedback regulation of cholinergic modulation based on activity in region CA1 sets the appropriate dynamics of learning for novel associations, and recall for familiar associations.
乙酰胆碱（ACh）可能会将皮质功能的动态调节至适合学习新信息的状态。在梨状皮质假定的联想记忆功能模型中，ACh对内在而非传入纤维突触传递的选择性抑制可防止先前输入的回忆干扰新输入的学习（哈塞尔莫，1993年）。选择性胆碱能抑制在海马结构中可能发挥类似作用，其中放射层（s. rad）的谢弗侧支突触可能存储CA3区活动与终止于腔隙-分子层（s. l-m）的CA1区内嗅皮质输入之间的关联。CA1区的一个计算模型预测，为实现谢弗侧支有效的联想记忆功能，胆碱能对突触传递的抑制在s. rad中应比对s. l-m更强。在海马脑片制备中，我们测试了胆碱能激动剂卡巴胆碱（0.01 - 500微摩尔）对s. rad和s. l-m中突触传递的影响。刺激电极和记录电极同时置于这两层中，从而能够在每个脑片的同一灌流过程中分析卡巴胆碱对两层中突触电位的影响。在所有高于1微摩尔的浓度下，卡巴胆碱对s. rad中刺激诱发的兴奋性突触后电位（EPSP）的抑制作用明显强于s. l-m。在100微摩尔时，s. rad中EPSP的起始斜率被抑制了89.1±3.0%，而在s. l-m中仅被抑制了40.1±4.1%。毒蕈碱拮抗剂阿托品（1微摩尔）可阻断两层中的胆碱能抑制。这些数据支持了这样一种假说，即谢弗侧支的突触修饰可能存储CA3区活动与来自内嗅皮质的CA1区传入输入之间的关联。在模拟中，基于CA1区活动的胆碱能调制的反馈调节为新关联的学习和熟悉关联的回忆设定了适当的动态。
