Brandalise Federico, Chéreau Ronan, Chen I-Wen, van Oorschot David, Morin Raig Claudia, Bawa Tanika, Mule Nandkishor, Pagès Stéphane, Markopoulos Foivos, Holtmaat Anthony
Department of Basic Neurosciences and the Geneva University Neurocenter, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland.
Division of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Nat Commun. 2025 Jul 1;16(1):5663. doi: 10.1038/s41467-025-60835-w.
The apical dendrites of layer (L) 2/3 pyramidal neurons in the mouse somatosensory cortex integrate synaptic input from long-range projections. Among those, inputs from the higher-order thalamic posteromedial nucleus may facilitate sensory-evoked cortical activity, but it remains elusive how this role emerges. Here we show using ex vivo dendritic recordings that these projections provide dense synaptic input to broad tufted neurons residing predominantly in L2 and cooperate with other inputs to produce NMDA spikes. They have the unique capacity to block two-pore domain potassium leak channels via group 1 metabotropic glutamate receptor (mGluRI) signaling, which increases excitability. Slender tufted L2/3 neurons and other long-range projections fail to invoke these mechanisms. In vivo imaging of calcium signals confirms the presence of mGluRI-dependent modulation of feedback-mediated spiking in L2. Our results imply that higher-order thalamocortical projections regulate neuronal excitability in a cell type and input-selective manner through fast NMDAR and mGluRI-dependent mechanisms.
小鼠体感皮层第2/3层锥体神经元的顶端树突整合来自长距离投射的突触输入。其中，来自高级丘脑后内侧核的输入可能促进感觉诱发的皮层活动，但其作用是如何产生的仍不清楚。在这里，我们使用离体树突记录表明，这些投射为主要位于第2层的广泛簇状神经元提供密集的突触输入，并与其他输入协同产生NMDA尖峰。它们具有通过1型代谢型谷氨酸受体（mGluRI）信号传导阻断双孔域钾泄漏通道的独特能力，从而增加兴奋性。细长簇状的第2/3层神经元和其他长距离投射无法引发这些机制。钙信号的体内成像证实了第2层中存在mGluRI依赖性的反馈介导尖峰调制。我们的结果表明，高级丘脑皮质投射通过快速NMDAR和mGluRI依赖性机制以细胞类型和输入选择性方式调节神经元兴奋性。
