Quaresima Alessio, Fitz Hartmut, Hagoort Peter, Duarte Renato
Neurobiology of Language Department, Max Planck Institute for Psycholinguistics, 6565 XD, Nijmegen, The Netherlands
Institut de l'Audition, Institut Pasteur, Paris 75012, France.
J Neurosci. 2025 Jun 25;45(26):e1701242025. doi: 10.1523/JNEUROSCI.1701-24.2025.
Changes in the activity profile of cortical neurons are due to effects at the scale of local and long-range networks. Accordingly, abrupt transitions in the state of cortical neurons-a phenomenon known as Up-Down states (UDS)-have been attributed to variation in the activity of afferent neurons. However, cellular physiology and morphology may also play a role in causing UDS. This study examines the impact of dendritic nonlinearities, particularly those mediated by voltage-dependent NMDA receptors, on the response of cortical neurons to balanced excitatory/inhibitory synaptic inputs. Using a neuron model with two segregated dendritic compartments, we compared cells with and without dendritic nonlinearities. NMDA receptors boosted somatic firing in the balanced condition and increased the correlation between membrane potentials across the compartments of the neuron model. Dendritic nonlinearities elicited strong bimodality in the distribution of the somatic potential when the cell was driven with cortical-like input. Moreover, dendritic nonlinearities could detect small input fluctuations and lead to UDS whose statistics and dynamics closely resemble electrophysiological data. UDS also occurred in recurrent networks with oscillatory firing activity, as in anaesthetized animal models, when dendritic NMDA receptors were partially disabled. These findings suggest that there is a dissociation between cellular and network-level features that could both contribute to the emergence of UDS. Our study highlights the complex interplay between dendritic integration and activity-driven dynamics in the origin of cortical bistability.
皮层神经元活动模式的变化归因于局部和远程网络层面的影响。相应地，皮层神经元状态的突然转变——一种被称为上下状态（UDS）的现象——被认为是传入神经元活动变化所致。然而，细胞生理学和形态学在引发UDS方面也可能发挥作用。本研究考察了树突非线性，特别是由电压依赖性NMDA受体介导的树突非线性，对皮层神经元对平衡兴奋性/抑制性突触输入反应的影响。使用具有两个分离树突节段的神经元模型，我们比较了有无树突非线性的细胞。在平衡状态下，NMDA受体增强了体细胞放电，并增加了神经元模型各节段膜电位之间的相关性。当细胞由类似皮层的输入驱动时，树突非线性在体细胞电位分布中引发了强烈的双峰性。此外，树突非线性能够检测到小的输入波动，并导致其统计和动力学与电生理数据非常相似的UDS。当树突NMDA受体部分失活时，UDS也会出现在具有振荡放电活动的循环网络中，就像在麻醉动物模型中一样。这些发现表明，细胞和网络层面的特征之间存在分离，二者都可能导致UDS的出现。我们的研究突出了树突整合与活动驱动动力学在皮层双稳态起源中的复杂相互作用。
