title: Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation.
abstract: The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state. PAPERCLIP.
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, W12 0NN London, UK.
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Matthews
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Nieh
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Vander Weele
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Halbert
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Roma V
authors.initials: RV
authors.lastname: Pradhan
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Ariella S
authors.initials: AS
authors.lastname: Yosafat
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Glober
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Ehsan M
authors.initials: EM
authors.lastname: Izadmehr
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Rain E
authors.initials: RE
authors.lastname: Thomas
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Gabrielle D
authors.initials: GD
authors.lastname: Lacy
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Craig P
authors.initials: CP
authors.lastname: Wildes
authors.affiliation: Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, W12 0NN London, UK. Electronic address: mark.ungless@imperial.ac.uk.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ungless
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: kaytye@mit.edu.
authors.forename: Kay M
authors.initials: KM
authors.lastname: Tye
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000473:pathology*; D065847:Dorsal Raphe Nucleus / Q000473:pathology* / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008132:Loneliness; D008297:Male; D051379:Mice; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D012201:Reward; D013569:Synapses; D017557:Ventral Tegmental Area / Q000502:physiology
chemical_list: D018698:Glutamic Acid; D004298:Dopamine