The Edmond and Lily Safra Center for Brain Sciences (ELSC) and The Department of Neurobiology, The Life Sciences Institute, The Hebrew University of Jerusalem, Jerusalem, Israel 91904.
The Edmond and Lily Safra Center for Brain Sciences (ELSC) and The Department of Neurobiology, The Life Sciences Institute, The Hebrew University of Jerusalem, Jerusalem, Israel 91904
J Neurosci. 2022 Feb 16;42(7):1184-1195. doi: 10.1523/JNEUROSCI.1470-21.2021. Epub 2021 Dec 10.
Nonlinear synaptic integration in dendrites is a fundamental aspect of neural computation. One such key mechanism is the Ca spike at the apical tuft of pyramidal neurons. Characterized by a plateau potential sustained for tens of milliseconds, the Ca spike amplifies excitatory input, facilitates somatic action potentials (APs), and promotes synaptic plasticity. Despite its essential role, the mechanisms regulating it are largely unknown. Using a compartmental model of a layer 5 pyramidal cell (L5PC), we explored the plateau and termination phases of the Ca spike under input current perturbations, long-step current-injections, and variations in the dendritic high-voltage-activated Ca conductance (that occur during cholinergic modulation). We found that, surprisingly, timed excitatory input can shorten the Ca spike duration while inhibitory input can either elongate or terminate it. A significant elongation also occurs when the high-voltage-activated Ca channels (Ca) conductance is increased. To mechanistically understand these phenomena, we analyzed the currents involved in the spike. The plateau and termination phases are almost exclusively controlled by the Ca inward current and the I outward K current. We reduced the full model to a single-compartment model that faithfully preserved the responses of the Ca spike to interventions and consisted of two dynamic variables: the membrane potential and the K-channel activation level. A phase-plane analysis of the reduced model provides testable predictions for modulating the Ca spike and reveals various dynamical regimes that explain the robust nature of the spike. Regulating the duration of the Ca spike significantly impacts the cell synaptic-plasticity window and, as we show, its input-output relationship. Pyramidal neurons are the cortex's principal projection neurons. In their apical tuft, dendritic Ca spikes significantly impact information processing, synaptic plasticity, and the cell's input-output relationship. Therefore, it is essential to understand the mechanisms regulating them. Using a compartmental model of a layer 5 pyramidal cell (L5PC), we explored the Ca spike responses to synaptic perturbations and cholinergic modulation. We showed a counterintuitive phenomenon: early excitatory input shortens the spike, whereas weak inhibition elongates it. Also, we demonstrated that acetylcholine (ACh) extends the spike. Through a reduced model containing only the membrane potential and the K-channel activation level, we explained these phenomena using a phase-plane analysis. Our work provides new information about the robustness of the Ca spike and its controlling mechanisms.
树突中的非线性突触整合是神经计算的一个基本方面。其中一个关键机制是顶树突锥体神经元中的钙峰。钙峰的特征是持续数十毫秒的平台电位，它放大兴奋性输入，促进体积极化电位 (AP)，并促进突触可塑性。尽管它具有重要作用，但调节它的机制在很大程度上是未知的。使用 5 层锥体神经元 (L5PC) 的分区模型，我们在输入电流扰动、长步电流注入和树突高电压激活钙电导变化下 (在胆碱能调制期间发生) ，探索了钙峰的平台和终止阶段。令人惊讶的是，我们发现，定时的兴奋性输入可以缩短钙峰的持续时间，而抑制性输入可以延长或终止它。当高电压激活钙通道 (Ca) 电导增加时，也会发生显著的延长。为了从机制上理解这些现象，我们分析了涉及峰的电流。平台和终止阶段几乎完全由钙内向电流和 I 外向 K 电流控制。我们将全模型简化为一个单室模型，该模型忠实地保留了钙峰对干预的反应，并由两个动态变量组成：膜电位和 K 通道激活水平。简化模型的相平面分析为调节钙峰提供了可测试的预测，并揭示了各种动力学状态，解释了钙峰的稳健性质。调节钙峰的持续时间会显著影响细胞的突触可塑性窗口，正如我们所展示的，还会影响其输入-输出关系。锥体神经元是皮质的主要投射神经元。在它们的顶树突中，树突钙峰对信息处理、突触可塑性和细胞的输入-输出关系有重大影响。因此，了解调节它们的机制至关重要。使用 5 层锥体神经元 (L5PC) 的分区模型，我们探索了钙峰对突触扰动和胆碱能调制的反应。我们展示了一个违反直觉的现象：早期的兴奋性输入会缩短峰，而弱抑制则会延长它。此外，我们还证明了乙酰胆碱 (ACh) 会延长峰。通过一个仅包含膜电位和 K 通道激活水平的简化模型，我们使用相平面分析解释了这些现象。我们的工作提供了关于钙峰的稳健性及其控制机制的新信息。
