Functional Principles of Posterior Septal Inputs to the Medial Habenula

The medial habenula (MHb) is an epithalamic hub contributing to expression and extinction of aversive states by bridging forebrain areas and midbrain monoaminergic centers. Although contradictory information exists regarding their synaptic properties, the physiology of the excitatory inputs to the M...

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Main Authors: Yo Otsu, Salvatore Lecca, Katarzyna Pietrajtis, Charly Vincent Rousseau, Païkan Marcaggi, Guillaume Pierre Dugué, Caroline Mailhes-Hamon, Manuel Mameli, Marco Alberto Diana
Format: Article
Language:English
Published: Elsevier 2018-01-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124717319010
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author Yo Otsu
Salvatore Lecca
Katarzyna Pietrajtis
Charly Vincent Rousseau
Païkan Marcaggi
Guillaume Pierre Dugué
Caroline Mailhes-Hamon
Manuel Mameli
Marco Alberto Diana
author_facet Yo Otsu
Salvatore Lecca
Katarzyna Pietrajtis
Charly Vincent Rousseau
Païkan Marcaggi
Guillaume Pierre Dugué
Caroline Mailhes-Hamon
Manuel Mameli
Marco Alberto Diana
author_sort Yo Otsu
collection DOAJ
description The medial habenula (MHb) is an epithalamic hub contributing to expression and extinction of aversive states by bridging forebrain areas and midbrain monoaminergic centers. Although contradictory information exists regarding their synaptic properties, the physiology of the excitatory inputs to the MHb from the posterior septum remains elusive. Here, combining optogenetics-based mapping with ex vivo and in vivo physiology, we examine the synaptic properties of posterior septal afferents to the MHb and how they influence behavior. We demonstrate that MHb cells receive sparse inputs producing purely glutamatergic responses via calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), heterotrimeric GluN2A-GluN2B-GluN1 N-methyl-D-aspartate (NMDA) receptors, and inhibitory group II metabotropic glutamate receptors. We describe the complex integration dynamics of these components by MHb cells. Finally, we combine ex vivo data with realistic afferent firing patterns recorded in vivo to demonstrate that efficient optogenetic septal stimulation in the MHb induces anxiolysis and promotes locomotion, contributing long-awaited evidence in favor of the importance of this septo-habenular pathway.
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spelling doaj.art-601b4beaf6ad4b49b843e5a8aa3059e92022-12-21T20:01:12ZengElsevierCell Reports2211-12472018-01-0122369370510.1016/j.celrep.2017.12.064Functional Principles of Posterior Septal Inputs to the Medial HabenulaYo Otsu0Salvatore Lecca1Katarzyna Pietrajtis2Charly Vincent Rousseau3Païkan Marcaggi4Guillaume Pierre Dugué5Caroline Mailhes-Hamon6Manuel Mameli7Marco Alberto Diana8Institut de Biologie de l’École Normale Supérieure, INSERM U1024, CNRS UMR8197, École Normale Supérieure, PSL Research University, Paris, FranceInstitut du Fer à Moulin, INSERM-UPMC UMR-S 839, Paris, FranceInstitut de Biologie de l’École Normale Supérieure, INSERM U1024, CNRS UMR8197, École Normale Supérieure, PSL Research University, Paris, FranceInstitut de Biologie de l’École Normale Supérieure, INSERM U1024, CNRS UMR8197, École Normale Supérieure, PSL Research University, Paris, FranceInstitut de Biologie de l’École Normale Supérieure, INSERM U1024, CNRS UMR8197, École Normale Supérieure, PSL Research University, Paris, FranceInstitut de Biologie de l’École Normale Supérieure, INSERM U1024, CNRS UMR8197, École Normale Supérieure, PSL Research University, Paris, FranceInstitut de Biologie de l’École Normale Supérieure, INSERM U1024, CNRS UMR8197, École Normale Supérieure, PSL Research University, Paris, FranceInstitut du Fer à Moulin, INSERM-UPMC UMR-S 839, Paris, FranceInstitut de Biologie de l’École Normale Supérieure, INSERM U1024, CNRS UMR8197, École Normale Supérieure, PSL Research University, Paris, FranceThe medial habenula (MHb) is an epithalamic hub contributing to expression and extinction of aversive states by bridging forebrain areas and midbrain monoaminergic centers. Although contradictory information exists regarding their synaptic properties, the physiology of the excitatory inputs to the MHb from the posterior septum remains elusive. Here, combining optogenetics-based mapping with ex vivo and in vivo physiology, we examine the synaptic properties of posterior septal afferents to the MHb and how they influence behavior. We demonstrate that MHb cells receive sparse inputs producing purely glutamatergic responses via calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), heterotrimeric GluN2A-GluN2B-GluN1 N-methyl-D-aspartate (NMDA) receptors, and inhibitory group II metabotropic glutamate receptors. We describe the complex integration dynamics of these components by MHb cells. Finally, we combine ex vivo data with realistic afferent firing patterns recorded in vivo to demonstrate that efficient optogenetic septal stimulation in the MHb induces anxiolysis and promotes locomotion, contributing long-awaited evidence in favor of the importance of this septo-habenular pathway.http://www.sciencedirect.com/science/article/pii/S2211124717319010posterior septummedial habenulaglutamatergic transmissioncalcium-permeable AMPA receptorsheterotrimeric NMDA receptorslocomotionanxiety
spellingShingle Yo Otsu
Salvatore Lecca
Katarzyna Pietrajtis
Charly Vincent Rousseau
Païkan Marcaggi
Guillaume Pierre Dugué
Caroline Mailhes-Hamon
Manuel Mameli
Marco Alberto Diana
Functional Principles of Posterior Septal Inputs to the Medial Habenula
Cell Reports
posterior septum
medial habenula
glutamatergic transmission
calcium-permeable AMPA receptors
heterotrimeric NMDA receptors
locomotion
anxiety
title Functional Principles of Posterior Septal Inputs to the Medial Habenula
title_full Functional Principles of Posterior Septal Inputs to the Medial Habenula
title_fullStr Functional Principles of Posterior Septal Inputs to the Medial Habenula
title_full_unstemmed Functional Principles of Posterior Septal Inputs to the Medial Habenula
title_short Functional Principles of Posterior Septal Inputs to the Medial Habenula
title_sort functional principles of posterior septal inputs to the medial habenula
topic posterior septum
medial habenula
glutamatergic transmission
calcium-permeable AMPA receptors
heterotrimeric NMDA receptors
locomotion
anxiety
url http://www.sciencedirect.com/science/article/pii/S2211124717319010
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