Cell Reports
Volume 22, Issue 3, 16 January 2018, Pages 693-705
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Article
Functional Principles of Posterior Septal Inputs to the Medial Habenula

https://doi.org/10.1016/j.celrep.2017.12.064Get rights and content
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Highlights

  • Medial habenular (MHb) neurons receive sparse inputs from the posterior septum (PS)

  • PS afferents to the MHb function in a purely glutamatergic mode

  • Excitatory ionotropic and inhibitory metabotropic receptors convey PS inputs in the MHb

  • PS activation in the MHb increases locomotion and induces anxiolysis

Summary

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.

Keywords

posterior septum
medial habenula
glutamatergic transmission
calcium-permeable AMPA receptors
heterotrimeric NMDA receptors
locomotion
anxiety

Cited by (0)

3

Present address: Institut du Fer à Moulin, INSERM-UPMC UMR-S 839, Paris, France

4

Present address: Department of Fundamental Neuroscience, University of Lausanne, Lausanne, Switzerland

5

Present address: Sainsbury Wellcome Centre for Neural Circuits and Behaviour, University College London, London W1T 4JG, UK

6

Present address: INMED/INSERM U901, Parc scientifique de Luminy, 163 route de Luminy, Marseille 13009, France

7

Present address: Sorbonne Universités, UPMC Université Paris 06, INSERM, CNRS, Neurosciences Paris Seine-Institut de Biologie Paris Seine (NPS-IBPS), 75005 Paris, France

8

Lead Contact