Thalamocortical feedback selectively controls pyramidal neuron excitability

Article Article scientifique Article Thalamocortical feedback selectively controls pyramidal neuron excitability eng 2025-07-01 author Brandalise Federico 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. 910962 author Chereau Ronan 0000-0002-2359-3086 Department of Basic Neurosciences and the Geneva University Neurocenter, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland. 829563 Département de neurosciences fondamentales (NEUFO) author Chen I-Wen 0000-0003-0598-7230 Department of Basic Neurosciences and the Geneva University Neurocenter, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland. 403507 Département de neurosciences fondamentales (NEUFO) author Van Oorschot David 0009-0001-8557-4200 Department of Basic Neurosciences and the Geneva University Neurocenter, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland. 983671 Département de neurosciences fondamentales (NEUFO) author Morin Raig Claudia Cristina Patricia 0009-0005-1087-1090 Department of Basic Neurosciences and the Geneva University Neurocenter, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland. 963250 author Bawa Tanika 0000-0002-1368-0346 Department of Basic Neurosciences and the Geneva University Neurocenter, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland. 857517 author Mule Nandkishor Kisanrao 0000-0001-8429-2490 Department of Basic Neurosciences and the Geneva University Neurocenter, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland. 911317 author Pages Stéphane Department of Basic Neurosciences and the Geneva University Neurocenter, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland.,WYSS Center, Campus Biotech, Geneva, Switzerland. 543062 author Markopoulos Foivos Department of Basic Neurosciences and the Geneva University Neurocenter, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland. 766031 author Holtmaat Antonius 0000-0002-7577-0769 Department of Basic Neurosciences and the Geneva University Neurocenter, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland. anthony.holtmaat@unige.ch. 661031 Département de neurosciences fondamentales (NEUFO) Anthony Holtmaat 5663 10.1038/s41467-025-60835-w 40595546 2041-1723 PMC12215560 https://www.nature.com/articles/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. Action Potentials / physiology Animals Dendrites / metabolism Dendrites / physiology Feedback, Physiological Female Male Mice Mice, Inbred C57BL Pyramidal Cells / metabolism Pyramidal Cells / physiology Receptors, Metabotropic Glutamate / metabolism Receptors, N-Methyl-D-Aspartate / metabolism Somatosensory Cortex / cytology Somatosensory Cortex / physiology Thalamus / physiology Dewey 616.8 Swiss National Science Foundation The role of paralemniscal circuits in cortical plasticity and perception 173125 CH Projects Swiss National Science Foundation Cortical synaptic circuit mechanisms for perceptual function and learning 204562 CH Projects 53 Département de neurosciences fondamentales 21A false 517 Les circuits neuronaux dans le néocortex des mammifères 855 https://zenodo.org/records/10210325 Nature communications 16 1 0e4a956c-cf17-4b9a-b33d-1251a7b60e03 Article (Published version) Public Brandalise2025_ThalamocorticalFeedb.pdf 13483183 application/pdf CC BY-4.0 a3811dc1929a17cd512b04d0384157e1c9df7c9d91fb34d324b6f4b70ba9514b be237529-3df2-41b4-9159-288cfb25c025 Supplemental data Public 41467_2025_60835_MOESM1_ESM.pdf 16154137 application/pdf 669cb79c3321c6482fb592488aca7338fe12a311f36b56c1e40290ed7e825b85 openAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Thalamocortical feedback selectively controls pyramidal neuron excitability	Nature communications			2025	18	648

Archive ouverte UNIGE

Van Oorschot, David