title: mGluR-LTD at Excitatory and Inhibitory Synapses in the Lateral Habenula Tunes Neuronal Output.
abstract: Excitatory and inhibitory transmission onto lateral habenula (LHb) neurons is instrumental for the expression of positive and negative motivational states. However, insights into the molecular mechanisms modulating synaptic transmission and the repercussions for neuronal activity within the LHb remain elusive. Here, we report that, in mice, activation of group I metabotropic glutamate receptors triggers long-term depression at excitatory (eLTD) and inhibitory (iLTD) synapses in the LHb. mGluR-eLTD and iLTD rely on mGluR1 and PKC signaling. However, mGluR-dependent adaptations of excitatory and inhibitory synaptic transmission differ in their expression mechanisms. mGluR-eLTD occurs via an endocannabinoid receptor-dependent decrease in glutamate release. Conversely, mGluR-iLTD occurs postsynaptically through PKC-dependent reduction of β2-containing GABAA-R function. Finally, mGluR-dependent plasticity of excitation or inhibition decides the direction of neuronal firing, providing a synaptic mechanism to bidirectionally control LHb output. We propose mGluR-LTD as a cellular substrate that underlies LHb-dependent encoding of opposing motivational states.
authors.affiliation: Institut du Fer à Moulin, 75005 Paris, France; Inserm, UMR-S 839, 75005 Paris, France; Université Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Kristina
authors.initials: K
authors.lastname: Valentinova
authors.affiliation: Institut du Fer à Moulin, 75005 Paris, France; Inserm, UMR-S 839, 75005 Paris, France; Université Pierre et Marie Curie, 75005 Paris, France. Electronic address: manuel.mameli@inserm.fr.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mameli
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D063388:Endocannabinoids / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D019262:Habenula / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D061251:Primary Cell Culture; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000502:physiology; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D063388:Endocannabinoids; D043882:Receptors, Cannabinoid; D011963:Receptors, GABA-A; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid; D011493:Protein Kinase C