Optogenetic recruitment of dorsal raphe serotonergic neurons acutely decreases mechanosensory responsivity in behaving mice

Guillaume P Dugué; Magor L Lörincz; Eran Lottem; Enrica Audero; Sara Matias; Patricia A Correia; Clément Léna; Zachary F Mainen

doi:10.1371/journal.pone.0105941

Optogenetic recruitment of dorsal raphe serotonergic neurons acutely decreases mechanosensory responsivity in behaving mice

PLoS One. 2014 Aug 22;9(8):e105941. doi: 10.1371/journal.pone.0105941. eCollection 2014.

Authors

Guillaume P Dugué¹, Magor L Lörincz², Eran Lottem³, Enrica Audero³, Sara Matias³, Patricia A Correia³, Clément Léna⁴, Zachary F Mainen³

Affiliations

¹ Champalimaud Neuroscience Programme, Champalimaud Center for the Unknown, Lisbon, Portugal; Institut de Biologie de l'Ecole Normale Supérieure, Centre National de la Recherche Scientifique (CNRS) UMR8197, Institut National de la Santé et de la Recherche Médicale (INSERM) U1024, Paris, France.
² Champalimaud Neuroscience Programme, Champalimaud Center for the Unknown, Lisbon, Portugal; MTA-SZTE Research Group for Cortical Microcircuits, Department of Physiology, University of Szeged, Szeged, Hungary.
³ Champalimaud Neuroscience Programme, Champalimaud Center for the Unknown, Lisbon, Portugal.
⁴ Institut de Biologie de l'Ecole Normale Supérieure, Centre National de la Recherche Scientifique (CNRS) UMR8197, Institut National de la Santé et de la Recherche Médicale (INSERM) U1024, Paris, France.

Abstract

The inhibition of sensory responsivity is considered a core serotonin function, yet this hypothesis lacks direct support due to methodological obstacles. We adapted an optogenetic approach to induce acute, robust and specific firing of dorsal raphe serotonergic neurons. In vitro, the responsiveness of individual dorsal raphe serotonergic neurons to trains of light pulses varied with frequency and intensity as well as between cells, and the photostimulation protocol was therefore adjusted to maximize their overall output rate. In vivo, the photoactivation of dorsal raphe serotonergic neurons gave rise to a prominent light-evoked field response that displayed some sensitivity to a 5-HT1A agonist, consistent with autoreceptor inhibition of raphe neurons. In behaving mice, the photostimulation of dorsal raphe serotonergic neurons produced a rapid and reversible decrease in the animals' responses to plantar stimulation, providing a new level of evidence that serotonin gates sensory-driven responses.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
Animals
Behavior, Animal
Dorsal Raphe Nucleus / drug effects
Dorsal Raphe Nucleus / physiology*
Mechanotransduction, Cellular
Mice, Transgenic
Neurons / drug effects
Neurons / physiology*
Optogenetics / methods*
Organ Culture Techniques
Photic Stimulation
Serotonin / metabolism*
Serotonin 5-HT1 Receptor Agonists / pharmacology

Substances

Serotonin 5-HT1 Receptor Agonists
Serotonin
8-Hydroxy-2-(di-n-propylamino)tetralin

Associated data

Dryad/10.5061/dryad.NH437

Grants and funding

This work was supported by an European Research Council grant to ZM (N ° 250334), an Intra-European Marie Curie postdoctoral fellowship to GD (N ° 220098), a Human Frontier Science Programme postdoctoral fellowship to MLL (N ° LT001009/2010L), a Human Frontier Science Programme postdoctoral fellowship to EL (N ° LT000881/2011L) and an Agence Nationale pour la Recherche grant to CL (Sensocode 11-BSV4-028). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.