Ritzau-Jost Andreas, Rajayer Salil, Nerlich Jana, Maciag Filip, John Alexandra, Russier Michael, Sabater Victoria Gonzalez, Steiger Luke J, Coq Jacques-Olivier, Eilers Jens, Engelhardt Maren, Burrone Juan, Debanne Dominique, Heine Martin, Smith Stephen M, Hallermann Stefan
Carl-Ludwig-Institute of Physiology, Faculty of Medicine, Leipzig University, Leipzig, 04103, Germany.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Oregon Health and Science University, Portland, Oregon, 97239-3098, USA.
bioRxiv. 2025 May 15:2025.05.09.653135. doi: 10.1101/2025.05.09.653135.
Homeostatic plasticity preserves neuronal activity against perturbations. Recently, somatic action potential broadening was proposed as a key homeostatic adaptation to chronic inactivity in neocortical neurons. Since action potential shape critically controls calcium entry and neuronal function, broadening provides an attractive homeostatic feedback mechanism to regulate activity. Here, we report that chronic inactivity induced by sodium channel block does not broaden action potentials in neocortical neurons under a wide range of conditions. In contrast, action potentials were broadened in CA3 neurons of organotypic hippocampal cultures by chronic sodium channel block and in hippocampal dissociated cultures by chronic synaptic block. Mechanistically, BK-type potassium channels were proposed to underly inactivity-induced action potential broadening. However, BK channels did not affect action potential duration in our recordings. Our results indicate that action potential broadening can occur in specific neurons and conditions but is not a general mechanism of homeostatic plasticity in cultured neurons.
稳态可塑性可保护神经元活动免受干扰。最近，体细胞动作电位展宽被认为是新皮层神经元对慢性失活的一种关键稳态适应。由于动作电位形状严格控制钙内流和神经元功能，展宽提供了一种有吸引力的稳态反馈机制来调节活动。在此，我们报告，在广泛条件下，钠通道阻断诱导的慢性失活不会使新皮层神经元的动作电位展宽。相反，在器官型海马培养物的CA3神经元中，慢性钠通道阻断会使动作电位展宽，而在海马解离培养物中，慢性突触阻断会使动作电位展宽。从机制上讲，BK型钾通道被认为是失活诱导的动作电位展宽的基础。然而，在我们的记录中，BK通道并不影响动作电位持续时间。我们的结果表明，动作电位展宽可在特定神经元和条件下发生，但不是培养神经元中稳态可塑性的一般机制。
