期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 25, 页码 12488-12493出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1903334116
关键词
habenula; stress; reward; anhedonia; prediction error
资金
- NIH [RO1MH091119]
- Shiley-Marcos endowment
Neuronal activity in the lateral habenula (LHb), a brain region implicated in depression [C. D. Proulx, O. Hikosaka, R. Malinow, Nat. Neurosci. 17,1146-1152 (2014)], decreases during reward and increases during punishment or reward omission [M. Matsumoto, O. Hikosaka, Nature 447,1111-1115 (2007)]. While stress is a major risk factor for depression and strongly impacts the LHb, its effect on LHb reward signals is unknown. Here we image LHb neuronal activity in behaving mice and find that acute stress transforms LHb reward responses into punishment-like neural signals; punishment-like responses to reward omission also increase. These neural changes matched the onset of anhedonic behavior and were specific to LHb neurons that distinguished reward and its omission. Thus, stress distorts LHb responsivity to positive and negative feedback, which could bias individuals toward negative expectations, a key aspect of the proposed pathogenesis of depression [A. T. Beck, Depression: Clinical, Experimental, and Theoretical Aspects, sixth Ed (1967)].
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