Autor: |
Garcia-Garcia AL; Dranovsky-Leonardo (ADL) Lab, Department of Psychiatry, Division of Integrative Neuroscience, Columbia University and the New York State Psychiatric Institute, New York, NY, USA. ag3149@cumc.columbia.edu., Canetta S; Department of Psychiatry, Columbia University, New York, NY, USA., Stujenske JM; Department of Psychiatry, Division of Integrative Neuroscience, Columbia University and the New York State Psychiatric Institute, New York, NY, USA., Burghardt NS; Department of Psychology, Hunter College, City University of New York, New York, NY, USA., Ansorge MS; Department of Psychiatry, Columbia University, New York, NY, USA., Dranovsky A; Dranovsky-Leonardo (ADL) Lab, Department of Psychiatry, Division of Integrative Neuroscience, Columbia University and the New York State Psychiatric Institute, New York, NY, USA. ad722@cumc.columbia.edu., Leonardo ED; Dranovsky-Leonardo (ADL) Lab, Department of Psychiatry, Division of Integrative Neuroscience, Columbia University and the New York State Psychiatric Institute, New York, NY, USA. el367@cumc.columbia.edu. |
Abstrakt: |
Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus of the stria terminalis (BNST), a major subdivision of the extended amygdala that has been proposed to regulate responses to anxiogenic environments in humans and rodents. While the dorsal part of the BNST (dBNST) receives dense 5-HT innervation, whether and how 5-HT in the dBNST normally modulates anxiety remains unclear. Using optogenetics, we demonstrate that activation of 5-HT terminals in the dBNST reduces anxiety in a highly anxiogenic environment. Further analysis revealed that optogenetic inhibition of 5-HT inputs into the dBNST increases anxiety in a less anxiogenic environment. We found that 5-HT predominantly hyperpolarizes dBNST neurons, reducing their activity in a manner that can be blocked by a 5-HT 1A antagonist. Finally, we demonstrate that activation of 5-HT 1A receptors in the dBNST is necessary for the anxiolytic effect observed following optogenetic stimulation of 5-HT inputs into the dBNST. These data reveal that 5-HT release in the dBNST modulates anxiety-like behavior via 5-HT 1A receptors under naturalistic conditions. |