Serotonin 1B Receptors Regulate Prefrontal Function by Gating Callosal and Hippocampal Inputs

TY - JOUR

T1 - Serotonin 1B Receptors Regulate Prefrontal Function by Gating Callosal and Hippocampal Inputs

AU - Kjaerby, Celia

AU - Athilingam, Jegath

AU - Robinson, Sarah E

AU - Iafrati, Jillian

AU - Sohal, Vikaas S

N1 - Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2016/12/13

Y1 - 2016/12/13

N2 - 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.

AB - 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.

KW - Animals

KW - Behavior, Animal/physiology

KW - Hippocampus/drug effects

KW - Maze Learning/drug effects

KW - Mice

KW - Prefrontal Cortex/metabolism

KW - Receptor, Serotonin, 5-HT1B/metabolism

KW - Serotonin/genetics

KW - Serotonin 5-HT1 Receptor Agonists/administration & dosage

KW - Synapses/drug effects

KW - Theta Rhythm/physiology

U2 - 10.1016/j.celrep.2016.11.036

DO - 10.1016/j.celrep.2016.11.036

M3 - Journal article

C2 - 27974203

SN - 2211-1247

VL - 17

SP - 2882

EP - 2890

JO - Cell Reports

JF - Cell Reports

IS - 11

ER -