title: Sleep slow wave-related homo and heterosynaptic LTD of intrathalamic GABAAergic synapses: involvement of T-type Ca2+ channels and metabotropic glutamate receptors.
abstract: Slow waves of non-REM sleep are suggested to play a role in shaping synaptic connectivity to consolidate recently acquired memories and/or restore synaptic homeostasis. During sleep slow waves, both GABAergic neurons of the nucleus reticularis thalami (NRT) and thalamocortical (TC) neurons discharge high-frequency bursts of action potentials mediated by low-threshold calcium spikes due to T-type Ca(2+) channel activation. Although such activity of the intrathalamic network characterized by high-frequency firing and calcium influx is highly suited to modify synaptic efficacy, very little is still known about its consequences on intrathalamic synapse strength. Combining in vitro electrophysiological recordings and calcium imaging, here we show that the inhibitory GABAergic synapses between NRT and TC neurons of the rat somatosensory nucleus develop a long-term depression (I-LTD) when challenged by a stimulation paradigm that mimics the thalamic network activity occurring during sleep slow waves. The mechanism underlying this plasticity presents unique features as it is both heterosynaptic and homosynaptic in nature and requires Ca(2+) entry selectively through T-type Ca(2+) channels and activation of the Ca(2+)-activated phosphatase, calcineurin. We propose that during slow-wave sleep the tight functional coupling between GABAA receptors, calcineurin, and T-type Ca(2+) channels will elicit LTD of the activated GABAergic synapses when coupled with concomitant activation of metabotropic glutamate receptors postsynaptic to cortical afferences. This I-LTD may be a key element involved in the reshaping of the somatosensory information pathway during sleep.
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UM 119, Neuroscience Paris Seine (NPS), Paris F-75005, France, CNRS, UMR 8246, NPS, Paris F-75005, France, and INSERM, U1130, NPS, Paris F-75005, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Pigeat
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UM 119, Neuroscience Paris Seine (NPS), Paris F-75005, France, CNRS, UMR 8246, NPS, Paris F-75005, France, and INSERM, U1130, NPS, Paris F-75005, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Chausson
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UM 119, Neuroscience Paris Seine (NPS), Paris F-75005, France, CNRS, UMR 8246, NPS, Paris F-75005, France, and INSERM, U1130, NPS, Paris F-75005, France.
authors.forename: Fanny M
authors.initials: FM
authors.lastname: Dreyfus
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UM 119, Neuroscience Paris Seine (NPS), Paris F-75005, France, CNRS, UMR 8246, NPS, Paris F-75005, France, and INSERM, U1130, NPS, Paris F-75005, France.
authors.forename: Nathalie
authors.identifier: http://orcid.org/0000-0001-6705-9769
authors.initials: N
authors.lastname: Leresche
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, UM 119, Neuroscience Paris Seine (NPS), Paris F-75005, France, CNRS, UMR 8246, NPS, Paris F-75005, France, and INSERM, U1130, NPS, Paris F-75005, France regis.lambert@upmc.fr.
authors.forename: Régis C
authors.identifier: http://orcid.org/0000-0001-8972-1151
authors.initials: RC
authors.lastname: Lambert
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000502:physiology*; D059330:GABAergic Neurons / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013788:Thalamus / Q000502:physiology*
chemical_list: D020747:Calcium Channels, T-Type; D018094:Receptors, Metabotropic Glutamate
keywords: GABAA receptor; calcineurin; low-threshold calcium spike; nucleus reticularis thalami; synaptic plasticity; ventrobasal thalamic nucleus