Chronic CRH depletion from GABAergic, long-range projection neurons in the extended amygdala reduces dopamine release and increases anxiety

Nina Dedic; Claudia Kühne; Mira Jakovcevski; Jakob Hartmann; Andreas J Genewsky; Karina S Gomes; Elmira Anderzhanova; Max L Pöhlmann; Simon Chang; Adam Kolarz; Annette M Vogl; Julien Dine; Michael W Metzger; Bianca Schmid; Rafael C Almada; Kerry J Ressler; Carsten T Wotjak; Valery Grinevich; Alon Chen; Mathias V Schmidt; Wolfgang Wurst; Damian Refojo; Jan M Deussing

doi:10.1038/s41593-018-0151-z

Chronic CRH depletion from GABAergic, long-range projection neurons in the extended amygdala reduces dopamine release and increases anxiety

Nat Neurosci. 2018 Jun;21(6):803-807. doi: 10.1038/s41593-018-0151-z. Epub 2018 May 21.

Authors

Nina Dedic¹, Claudia Kühne¹, Mira Jakovcevski¹, Jakob Hartmann^{1

2}, Andreas J Genewsky¹, Karina S Gomes^{1

3}, Elmira Anderzhanova¹, Max L Pöhlmann¹, Simon Chang¹, Adam Kolarz¹, Annette M Vogl¹, Julien Dine¹, Michael W Metzger¹, Bianca Schmid¹, Rafael C Almada¹, Kerry J Ressler², Carsten T Wotjak¹, Valery Grinevich⁴, Alon Chen¹, Mathias V Schmidt¹, Wolfgang Wurst^{5

6

7}, Damian Refojo^{1

8}, Jan M Deussing⁹

Affiliations

¹ Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
² Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA, USA.
³ Laboratory of Neuropsychopharmacology, Paulista State University, Araraquara, Brazil.
⁴ Schaller Research Group on Neuropeptides, German Cancer Research Center, Central Institute of Mental Health, University of Heidelberg, Heidelberg, Germany.
⁵ Institute of Developmental Genetics, Helmholtz Zentrum München, Munich, Germany.
⁶ Technische Universität München, Chair of Developmental Genetics, Munich, Germany.
⁷ German Center for Neurodegenerative Diseases (DZNE), Site Munich, Munich, Germany.
⁸ Instituto de Investigacion en Biomedicina de Buenos Aires (IBioBA)-CONICET-Partner Institute of the Max Planck Society, Buenos Aires, Argentina.
⁹ Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany. [email protected].

Abstract

The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predominantly been studied in addiction and reward, while CRH-dopamine interactions in anxiety are scarcely understood. We describe a new population of CRH-expressing, GABAergic, long-range-projecting neurons in the extended amygdala that innervate the ventral tegmental area and alter anxiety following chronic CRH depletion. These neurons are part of a distinct CRH circuit that acts anxiolytically by positively modulating dopamine release.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amygdala / cytology
Amygdala / physiology*
Animals
Anxiety / psychology*
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / physiology
Corticotropin-Releasing Hormone / deficiency*
Corticotropin-Releasing Hormone / pharmacology
Dendritic Spines / ultrastructure
Dopamine / metabolism*
GABAergic Neurons / physiology*
Injections
Male
Mice
Mice, Knockout
Motor Activity
Optogenetics
Pain Perception
Receptors, Corticotropin-Releasing Hormone / metabolism
Ventral Tegmental Area / cytology
Ventral Tegmental Area / physiology

Substances

CRF receptor type 2
Receptors, Corticotropin-Releasing Hormone
CRF receptor type 1
Corticotropin-Releasing Hormone
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Camk2a protein, mouse
Dopamine

Abstract

Publication types

MeSH terms

Substances

Grants and funding