Anxiety Cells in a Hippocampal-Hypothalamic Circuit

Jessica C Jimenez; Katy Su; Alexander R Goldberg; Victor M Luna; Jeremy S Biane; Gokhan Ordek; Pengcheng Zhou; Samantha K Ong; Matthew A Wright; Larry Zweifel; Liam Paninski; René Hen; Mazen A Kheirbek

doi:10.1016/j.neuron.2018.01.016

Anxiety Cells in a Hippocampal-Hypothalamic Circuit

Neuron. 2018 Feb 7;97(3):670-683.e6. doi: 10.1016/j.neuron.2018.01.016. Epub 2018 Jan 31.

Authors

Affiliations

¹ Departments of Neuroscience, Psychiatry & Pharmacology, Columbia University, New York, NY, USA; Division of Integrative Neuroscience, Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA.
² Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.
³ Center for the Neural Basis of Cognition and Machine Learning Department, Carnegie Mellon University, Pittsburgh, PA, USA; Departments of Statistics and Neuroscience, Grossman Center for the Statistics of Mind, Center for Theoretical Neuroscience, Kavli Institute for Brain Science, and NeuroTechnology Center, Columbia University, New York, NY, USA.
⁴ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁵ Department of Pharmacology, University of Washington, Seattle, WA 98105, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98105, USA.
⁶ Departments of Statistics and Neuroscience, Grossman Center for the Statistics of Mind, Center for Theoretical Neuroscience, Kavli Institute for Brain Science, and NeuroTechnology Center, Columbia University, New York, NY, USA.
⁷ Departments of Neuroscience, Psychiatry & Pharmacology, Columbia University, New York, NY, USA; Division of Integrative Neuroscience, Department of Psychiatry, New York State Psychiatric Institute, New York, NY, USA. Electronic address: rh95@columbia.edu.
⁸ Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, USA; Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, CA, USA. Electronic address: mazen.kheirbek@ucsf.edu.

Abstract

The hippocampus is traditionally thought to transmit contextual information to limbic structures where it acquires valence. Using freely moving calcium imaging and optogenetics, we show that while the dorsal CA1 subregion of the hippocampus is enriched in place cells, ventral CA1 (vCA1) is enriched in anxiety cells that are activated by anxiogenic environments and required for avoidance behavior. Imaging cells defined by their projection target revealed that anxiety cells were enriched in the vCA1 population projecting to the lateral hypothalamic area (LHA) but not to the basal amygdala (BA). Consistent with this selectivity, optogenetic activation of vCA1 terminals in LHA but not BA increased anxiety and avoidance, while activation of terminals in BA but not LHA impaired contextual fear memory. Thus, the hippocampus encodes not only neutral but also valence-related contextual information, and the vCA1-LHA pathway is a direct route by which the hippocampus can rapidly influence innate anxiety behavior.

Keywords: anxiety; calcium imaging; ventral hippocampus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anxiety / physiopathology*
Avoidance Learning
Basolateral Nuclear Complex / physiology
CA1 Region, Hippocampal / physiology*
Conditioning, Classical
Fear
Hypothalamic Area, Lateral / physiology*
Male
Memory
Mice, Inbred C57BL
Neural Pathways / physiology
Neurons / physiology*
Optogenetics

Abstract

Publication types

MeSH terms

Grants and funding