title: Dynamic Analysis of the Conditional Oscillator Underlying Slow Waves in Thalamocortical Neurons.
abstract: During non-REM sleep the EEG shows characteristics waves that are generated by the dynamic interactions between cortical and thalamic oscillators. In thalamic neurons, low-threshold T-type Ca(2+) channels play a pivotal role in almost every type of neuronal oscillations, including slow (< 1 Hz) waves, sleep spindles and delta waves. The transient opening of T channels gives rise to the low threshold spikes (LTSs), and associated high frequency bursts of action potentials, that are characteristically present during sleep spindles and delta waves, whereas the persistent opening of a small fraction of T channels, (i.e., ITwindow) is responsible for the membrane potential bistability underlying sleep slow oscillations. Surprisingly thalamocortical (TC) neurons express a very high density of T channels that largely exceed the amount required to generate LTSs and therefore, to support certain, if not all, sleep oscillations. Here, to clarify the relationship between T current density and sleep oscillations, we systematically investigated the impact of the T conductance level on the intrinsic rhythmic activities generated in TC neurons, combining in vitro experiments and TC neuron simulation. Using bifurcation analysis, we provide insights into the dynamical processes taking place at the transition between slow and delta oscillations. Our results show that although stable delta oscillations can be evoked with minimal T conductance, the full range of slow oscillation patterns, including groups of delta oscillations separated by Up states ("grouped-delta slow waves") requires a high density of T channels. Moreover, high levels of T conductance ensure the robustness of different types of slow oscillations.
authors.affiliation: Neuroscience Division, School of Biosciences, Cardiff UniversityCardiff, UK; Lyon Neuroscience Research Center, Centre National de la Recherche Scientifique UMR 5292Lyon, France; Lyon Neuroscience Research Center, Institut National de la Santé et de la Recherche Médicale U1028Lyon, France; Faculté de Médecine, Université Claude BernardLyon, France; Sorbonne Universités, UPMC Université Paris 06, UM 119, Neuroscience Paris SeineParis, France; Centre National de la Recherche Scientifique, UMR 8246, Neuroscience Paris SeineParis, France; Institut National de la Santé et de la Recherche Médicale, U1130, Neuroscience Paris SeineParis, France.
authors.forename: François
authors.initials: F
authors.lastname: David
authors.affiliation: Neuroscience Division, School of Biosciences, Cardiff UniversityCardiff, UK; Department of Physiology and Biochemistry, University of MaltaMsida, Malta.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Crunelli
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, UM 119, Neuroscience Paris SeineParis, France; Centre National de la Recherche Scientifique, UMR 8246, Neuroscience Paris SeineParis, France; Institut National de la Santé et de la Recherche Médicale, U1130, Neuroscience Paris SeineParis, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Leresche
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, UM 119, Neuroscience Paris SeineParis, France; Centre National de la Recherche Scientifique, UMR 8246, Neuroscience Paris SeineParis, France; Institut National de la Santé et de la Recherche Médicale, U1130, Neuroscience Paris SeineParis, France.
authors.forename: Régis C
authors.initials: RC
authors.lastname: Lambert
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002415:Cats; D002540:Cerebral Cortex / Q000166:cytology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005829:Geniculate Bodies / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017711:Nonlinear Dynamics; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology
chemical_list: C570743:3,5-dichloro-N-(1-(2,2-dimethyltetrahydropyran-4-ylmethyl)-4-fluoropiperidin-4-ylmethyl)benzamide; D001549:Benzamides; D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D010880:Piperidines; D011724:Pyridazines; C107353:CGP 54626; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C049853:gabazine; D002118:Calcium
keywords: T-type calcium channels; bifurcation; computational modeling; delta waves; sleep slow wave; thalamus