Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits.
Separable actions of acetylcholine and noradrenaline on neuronal ensemble formation in hippocampal CA3 circuits.
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DOI：
10.1371/journal.pcbi.1009435
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发表时间：
2021-10
影响因子：
4.3
通讯作者：
Mellor JR
中科院分区：
文献类型：
--
作者：
Prince LY;Bacon T;Humphries R;Tsaneva-Atanasova K;Clopath C;Mellor JR
在海马体中，情景记忆被认为是由突触耦合的CA3锥体细胞的集合体的形成编码的，所述集合体由来自齿状回颗粒细胞的稀疏但强大的苔藓纤维输入驱动。神经调节剂乙酰胆碱和去甲肾上腺素分别被认为是决定记忆编码的显着性信号，但尚不清楚它们是否代表具有不同机制的不同信号。在这里，我们的实验表明，乙酰胆碱，去甲肾上腺素在较小程度上，抑制前馈抑制和增强的苔藓纤维通路中的兴奋-抑制比，但CA3经常性的网络特性只改变乙酰胆碱。我们探讨了这些研究结果的影响，对CA3合奏形成层次模型。在CA3锥体细胞的重建中，苔藓纤维通路去抑制促进突触后树突去极化，已知这是CA3-CA3复发性突触的突触可塑性所需的。我们进一步在CA3的尖峰神经网络模型中展示了乙酰胆碱特异性网络改变如何驱动快速重叠系综形成。因此，通过这些不同的机制，乙酰胆碱和去甲肾上腺素促进CA3中神经元集合的形成，这些神经元集合在海马中编码突出的情景记忆，但乙酰胆碱选择性地增强记忆存储的密度。大脑如何决定将哪些经历编码到记忆中以及丢弃哪些经历是神经科学中的一个基本问题。神经调质乙酰胆碱和去甲肾上腺素被认为分别在确定编码的内容中发挥核心作用，但它们的作用机制大多是未知的，并且这两种关键神经调质之间没有直接的比较。在这项研究中，我们研究了乙酰胆碱和去甲肾上腺素对负责记忆编码的关键回路，即海马齿状回-CA3微回路的影响。使用切片电生理学，我们测量乙酰胆碱和去甲肾上腺素对这个神经元网络内的关键突触和细胞节点的影响。然后，我们探讨了网络水平的影响，这些研究结果对神经元合奏形成层次的计算模型。基于所观察到的乙酰胆碱和去甲肾上腺素的生理效应，我们的模型预测，乙酰胆碱有助于有效地形成合奏内CA3具有高度的重叠，而去甲肾上腺素具有更有限的影响，并没有影响合奏形成的效率或重叠。
In the hippocampus, episodic memories are thought to be encoded by the formation of ensembles of synaptically coupled CA3 pyramidal cells driven by sparse but powerful mossy fiber inputs from dentate gyrus granule cells. The neuromodulators acetylcholine and noradrenaline are separately proposed as saliency signals that dictate memory encoding but it is not known if they represent distinct signals with separate mechanisms. Here, we show experimentally that acetylcholine, and to a lesser extent noradrenaline, suppress feed-forward inhibition and enhance Excitatory–Inhibitory ratio in the mossy fiber pathway but CA3 recurrent network properties are only altered by acetylcholine. We explore the implications of these findings on CA3 ensemble formation using a hierarchy of models. In reconstructions of CA3 pyramidal cells, mossy fiber pathway disinhibition facilitates postsynaptic dendritic depolarization known to be required for synaptic plasticity at CA3-CA3 recurrent synapses. We further show in a spiking neural network model of CA3 how acetylcholine-specific network alterations can drive rapid overlapping ensemble formation. Thus, through these distinct sets of mechanisms, acetylcholine and noradrenaline facilitate the formation of neuronal ensembles in CA3 that encode salient episodic memories in the hippocampus but acetylcholine selectively enhances the density of memory storage. How the brain decides which experiences to encode to memory and which to discard is a fundamental question in neuroscience. The neuromodulators acetylcholine and noradrenaline are believed to separately play a central role in determining what is encoded but the mechanisms by which they act are mostly unknown and there have been no direct comparisons made between these two critical neuromodulators. In this study, we investigate the effects of acetylcholine and noradrenaline on a key circuit responsible for the encoding of memories, namely, the dentate gyrus–CA3 microcircuit in the hippocampus. Using slice electrophysiology, we measure the effects of acetylcholine and noradrenaline on key synaptic and cellular nodes within this neuronal network. We then explore the network level implications of these findings on neuronal ensemble formation using a hierarchy of computational models. Based on the observed physiological effects of acetylcholine and noradrenaline, our models predict that acetylcholine facilitates efficient formation of ensembles within CA3 with a high degree of overlap whereas noradrenaline has more limited effects and no impact on the efficiency or overlap of ensemble formation.
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影响因子：
4.3
作者：
Bush D;Philippides A;Husbands P;O'Shea M
通讯作者：
O'Shea M
影响因子：
16.2
作者：
Gu Z;Yakel JL
通讯作者：
Yakel JL
影响因子：
2.5
作者：
Aston-Jones, G;Cohen, JD
通讯作者：
Cohen, JD
DOI：
10.1073/pnas.1317667111
发表时间：
2014-03-18
影响因子：
11.1
作者：
Brandalise, Federico;Gerber, Urs
通讯作者：
Gerber, Urs
影响因子：
16.6
作者：
Brandalise, Federico;Carta, Stefano;Helmchen, Fritjof;Lisman, John;Gerber, Urs
通讯作者：
Gerber, Urs