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Nat Commun. 2020 Mar 19;11(1):1466. doi: 10.1038/s41467-020-15035-z.

Excitatory VTA to DH projections provide a valence signal to memory circuits.

Author information

1
Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL, 60611, USA.
2
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
3
Department of Materials Science and Engineering, Northwestern University, 60208, Evanston, IL, USA.
4
College of Engineering, University of Missouri, Columbia, MO, 65211, USA.
5
Department of Physiology, Northwestern University, Chicago, IL, 60611, USA.
6
Biomedical Engineering, College of Engineering, The University of Arizona, Tucson, AZ, 85721, USA.
7
Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL, 60611, USA. j-radulovic@northwestern.edu.

Abstract

The positive or negative value (valence) of past experiences is normally integrated into neuronal circuits that encode episodic memories and plays an important role in guiding behavior. Here, we show, using mouse behavioral models, that glutamatergic afferents from the ventral tegmental area to the dorsal hippocampus (VTA→DH) signal negative valence to memory circuits, leading to the formation of fear-inducing context memories and to context-specific reinstatement of fear. To a lesser extent, these projections also contributed to opioid-induced place preference, suggesting a role in signaling positive valence as well, and thus a lack of dedicated polarity. Manipulations of VTA terminal activity were more effective in females and paralleled by sex differences in glutamatergic signaling. By prioritizing retrieval of negative and positive over neutral memories, the VTA→DH circuit can facilitate the selection of adaptive behaviors when current and past experiences are valence congruent.

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