title: Serotonin 1B Receptors Regulate Prefrontal Function by Gating Callosal and Hippocampal Inputs.
abstract: Both medial prefrontal cortex (mPFC) and serotonin play key roles in anxiety; however, specific mechanisms through which serotonin might act on the mPFC to modulate anxiety-related behavior remain unknown. Here, we use a combination of optogenetics and synaptic physiology to show that serotonin acts presynaptically via 5-HT1B receptors to selectively suppress inputs from the contralateral mPFC and ventral hippocampus (vHPC), while sparing those from mediodorsal thalamus. To elucidate how these actions could potentially regulate prefrontal circuit function, we infused a 5-HT1B agonist into the mPFC of freely behaving mice. Consistent with previous studies that have optogenetically inhibited vHPC-mPFC projections, activating prefrontal 5-HT1B receptors suppressed theta-frequency mPFC activity (4-12 Hz), and reduced avoidance of anxiogenic regions in the elevated plus maze. These findings suggest a potential mechanism, linking specific receptors, synapses, patterns of circuit activity, and behavior, through which serotonin may regulate prefrontal circuit function, including anxiety-related behaviors.
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Weil Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Sloan-Swartz Center for Theoretical Neurobiology, University of California, San Francisco, San Francisco, CA 94143-0444, USA.
authors.forename: Celia
authors.initials: C
authors.lastname: Kjaerby
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Weil Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Sloan-Swartz Center for Theoretical Neurobiology, University of California, San Francisco, San Francisco, CA 94143-0444, USA.
authors.forename: Jegath
authors.initials: J
authors.lastname: Athilingam
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Weil Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Sloan-Swartz Center for Theoretical Neurobiology, University of California, San Francisco, San Francisco, CA 94143-0444, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Robinson
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Weil Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Sloan-Swartz Center for Theoretical Neurobiology, University of California, San Francisco, San Francisco, CA 94143-0444, USA.
authors.forename: Jillian
authors.initials: J
authors.lastname: Iafrati
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Weil Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Sloan-Swartz Center for Theoretical Neurobiology, University of California, San Francisco, San Francisco, CA 94143-0444, USA. Electronic address: vikaas.sohal@ucsf.edu.
authors.forename: Vikaas S
authors.initials: VS
authors.lastname: Sohal
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000502:physiology; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013826:Theta Rhythm / Q000502:physiology
chemical_list: D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists; D012701:Serotonin
keywords: 5-HT1B receptor; anxiety; mediodorsal thalamus; prefrontal cortex; serotonin; ventral hippocampus