An extended amygdala-midbrain circuit controlling cocaine withdrawal-induced anxiety and reinstatement
Guilian Tian,
May Hui,
Desiree Macchia,
Pieter Derdeyn,
Alexandra Rogers,
Elizabeth Hubbard,
Chengfeng Liu,
Jose J. Vasquez,
Lara Taniguchi,
Katrina Bartas,
Sean Carroll,
Kevin T. Beier
Affiliations
Guilian Tian
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92617, USA
May Hui
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92617, USA
Desiree Macchia
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92617, USA
Pieter Derdeyn
Program in Mathematical, Computational, and Systems Biology, University of California, Irvine, Irvine, CA 92617, USA
Alexandra Rogers
Interdepartmental Neuroscience Program, University of California, Irvine, Irvine, CA 92617, USA
Elizabeth Hubbard
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92617, USA
Chengfeng Liu
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92617, USA
Jose J. Vasquez
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92617, USA
Lara Taniguchi
Interdepartmental Neuroscience Program, University of California, Irvine, Irvine, CA 92617, USA
Katrina Bartas
Program in Mathematical, Computational, and Systems Biology, University of California, Irvine, Irvine, CA 92617, USA
Sean Carroll
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92617, USA
Kevin T. Beier
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92617, USA; Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA 92617, USA; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92617, USA; Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92617, USA; Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA 92617, USA; UCI Mind, University of California, Irvine, Irvine, CA 92617, USA; Corresponding author
Summary: Although midbrain dopamine (DA) circuits are central to motivated behaviors, our knowledge of how experience modifies these circuits to facilitate subsequent behavioral adaptations is limited. Here we demonstrate the selective role of a ventral tegmental area DA projection to the amygdala (VTADA→amygdala) for cocaine-induced anxiety but not cocaine reward or sensitization. Our rabies virus-mediated circuit mapping approach reveals a persistent elevation in spontaneous and task-related activity of inhibitory GABAergic cells from the bed nucleus of the stria terminalis (BNST) and downstream VTADA→amygdala cells that can be detected even after a single cocaine exposure. Activity in BNSTGABA→midbrain cells is related to cocaine-induced anxiety but not reward or sensitization, and silencing this projection prevents development of anxiety during protracted withdrawal after cocaine administration. Finally, we observe that VTADA→amygdala cells are strongly activated after a challenge exposure to cocaine and that activity in these cells is necessary and sufficient for reinstatement of cocaine place preference.
