title: A class of GABAergic neurons in the prefrontal cortex sends long-range projections to the nucleus accumbens and elicits acute avoidance behavior.
abstract: GABAergic projections from the neocortex to subcortical structures have been poorly characterized. Using Dlxi12b-Cre mice, we found anatomical evidence for GABAergic neurons that project from the mouse medial prefrontal cortex (mPFC) to multiple subcortical targets. We used a combination of patch-clamp electrophysiology, optogenetics, and pharmacology to confirm that Dlxi12b-labeled projections from the mPFC to the nucleus accumbens (NAcc) release GABA and do not corelease glutamate. Furthermore, optogenetic stimulation of these GABAergic projections from mPFC to NAcc induces avoidance behavior in a real-time place preference task, suggesting that these long-range projecting GABAergic neurons can transmit aversive signals. Finally, we found evidence for heterogeneous histochemical and/or electrophysiological properties of long-range projecting GABAergic neurons in the mPFC. Some of these neurons were labeled in parvalbumin-Cre and vasoactive intestinal peptide-Cre mice. We also used a novel intersectional targeting strategy to label GABAergic neurons in the mPFC that project to NAcc and found that these neurons have fast-spiking properties and express parvalbumin. These results define possible functions and properties for a class of long-range projecting GABAergic neurons in the neocortex.
authors.affiliation: Department of Psychiatry, Center for Integrative Neuroscience, and Sloan-Swartz Center for Theoretical Neurobiology, University of California, San Francisco, San Francisco, California 94143-0444.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Lee
authors.affiliation: Department of Psychiatry.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vogt
authors.affiliation: Department of Psychiatry.
authors.forename: John L
authors.identifier: http://orcid.org/0000-0002-4414-7667
authors.initials: JL
authors.lastname: Rubenstein
authors.affiliation: Department of Psychiatry, Center for Integrative Neuroscience, and Sloan-Swartz Center for Theoretical Neurobiology, University of California, San Francisco, San Francisco, California 94143-0444 vikaas.sohal@ucsf.edu.
authors.forename: Vikaas S
authors.initials: VS
authors.lastname: Sohal
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D005260:Female; D059330:GABAergic Neurons / Q000166:cytology*; D008297:Male; D051379:Mice; D009434:Neural Pathways / Q000166:cytology* / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology* / Q000502:physiology; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology* / Q000502:physiology
keywords: GABA; aversion; nucleus accumbens; optogenetics; prefrontal cortex