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

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

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.

Publication types

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

MeSH terms

  • Animals
  • Conditioning, Classical
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / physiology
  • Fear / physiology
  • Female
  • Gene Silencing / drug effects
  • Glutamate Decarboxylase / metabolism
  • Glutamates / metabolism
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Kinetics
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Mice, Inbred C57BL
  • Morphine / pharmacology
  • Nerve Net / drug effects
  • Nerve Net / physiology*
  • Optogenetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Sex Characteristics
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / physiology*
  • Vesicular Glutamate Transport Protein 2 / metabolism

Substances

  • Glutamates
  • Receptors, N-Methyl-D-Aspartate
  • Vesicular Glutamate Transport Protein 2
  • Morphine
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2