General anesthesia activates a central anxiolytic center in the BNST
Dongye Lu,
Camille G. Uldry Lavergne,
Seonmi Choi,
Jaehong Park,
Jiwoo Kim,
Shengli Zhao,
Quinn Desimone,
Eva Lendaro,
Bin Chen,
Bao-Xia Han,
Fan Wang,
Nitsan Goldstein
Affiliations
Dongye Lu
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Camille G. Uldry Lavergne
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Seonmi Choi
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Jaehong Park
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA
Jiwoo Kim
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Shengli Zhao
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Quinn Desimone
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Eva Lendaro
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Bin Chen
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Bao-Xia Han
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Fan Wang
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Corresponding author
Nitsan Goldstein
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Summary: Low doses of general anesthetics like ketamine and dexmedetomidine have anxiolytic properties independent of their sedative effects, but the underlying mechanisms remain unclear. We discovered a population of GABAergic neurons in the oval division of the bed nucleus of the stria terminalis that are activated by multiple anesthetics and the anxiolytic drug diazepam (ovBNSTGA). The majority of ovBNSTGA neurons express neurotensin receptor 1 (Ntsr1) and form circuits with brain regions known to regulate anxiety and stress responses. Optogenetic activation of ovBNSTGA or ovBNSTNtsr1 neurons significantly attenuated anxiety-like behaviors in both naive animals and mice with inflammatory pain, while inhibition of these cells elevated anxiety. Activation of these neurons decreased heart rate and increased heart rate variability, suggesting that they reduce anxiety by modulating autonomic responses. Our study identifies ovBNSTGA/ovBNSTNtsr1 neurons as a common neural substrate mediating the anxiolytic effect of low-dose anesthetics and a potential therapeutic target for treating anxiety-related disorders.
