Ventromedial hypothalamic neurons control a defensive emotion state
Defensive behaviors reflect underlying emotion states, such as fear. The hypothalamus plays a role in such behaviors, but prevailing textbook views depict it as an effector of upstream emotion centers, such as the amygdala, rather than as an emotion center itself. We used optogenetic manipulations to probe the function of a specific hypothalamic cell type that mediates innate defensive responses. These neurons are sufficient to drive multiple defensive actions, and required for defensive behaviors in diverse contexts. The behavioral consequences of activating these neurons, moreover, exhibit properties characteristic of emotion states in general, including scalability, (negative) valence, generalization and persistence. Importantly, these neurons can also condition learned defensive behavior, further refuting long-standing claims that the hypothalamus is unable to support emotional learning and therefore is not an emotion center. These data indicate that the hypothalamus plays an integral role to instantiate emotion states, and is not simply a passive effector of upstream emotion centers.
© 2015, Kunwar et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. Received January 22, 2015. Accepted March 5, 2015. Published March 6, 2015. The authors thank Monica McCardle, Heeju Kim, Jung-Sook Kim and Xiaolin Da for technical assistance; Celine Chiu and Gina Mancuso for administrative support; and Robert Robertson, Brian Duistermars and Allan Wong for assistance with Matlab programming. We thank all members of Anderson lab for sharing regents and constructive discussion, Dr. Todd Anthony for providing viral reagents and Dr. Brad Lowell for SF1-Cre mice. We thank Ann Kennedy for assistance with data analyses and comments on manuscript. A. Steele and P. Paterson laboratories for discussion, sharing reagents and providing technical help. Dr. Baer, Dr. Lencioni, Jennifer Constanza, Jeffrey Cochrane, ruben Bayon, Ana Colon & Sarah Fitzgerald for ensuring animal welfare, care and husbandry. We would also like to thank R. Mooney, R. Adolphs, M. S. Fanselow, R. Malenka and A. Choe for constructive comments on the manuscript. Lastly, we would like to dedicate this manuscript to D. Robert J. Blanchard (d. 2013), who inspired this project and many others. Author contributions: PSK, Conception and design, Acquisition of data, Analysis and interpretation of data, Drafting or revising the article; MZ, Analysis and interpretation of data, Drafting or revising the article; RR, HC, MY, Acquisition of data, Analysis and interpretation of data; MM, Analysis and interpretation of looming data; DJA, Conception and design, Analysis and interpretation of data, Drafting or revising the article. Ethics: Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol 1602, 1552 & 1600.
Published - e06633.full.pdf