Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory

Proc Natl Acad Sci U S A. 2016 Dec 20;113(51):14835-14840. doi: 10.1073/pnas.1616515114. Epub 2016 Dec 7.


Dopamine neurotransmission in the dorsal hippocampus is critical for a range of functions from spatial learning and synaptic plasticity to the deficits underlying psychiatric disorders such as attention-deficit hyperactivity disorder. The ventral tegmental area (VTA) is the presumed source of dopamine in the dorsal hippocampus. However, there is a surprising scarcity of VTA dopamine axons in the dorsal hippocampus despite the dense network of dopamine receptors. We have explored this apparent paradox using optogenetic, biochemical, and behavioral approaches and found that dopaminergic axons and subsequent dopamine release in the dorsal hippocampus originate from neurons of the locus coeruleus (LC). Photostimulation of LC axons produced an increase in dopamine release in the dorsal hippocampus as revealed by high-performance liquid chromatography. Furthermore, optogenetically induced release of dopamine from the LC into the dorsal hippocampus enhanced selective attention and spatial object recognition via the dopamine D1/D5 receptor. These results suggest that spatial learning and memory are energized by the release of dopamine in the dorsal hippocampus from noradrenergic neurons of the LC. The present findings are critical for identifying the neural circuits that enable proper attention selection and successful learning and memory.

Keywords: attention; dopamine; hippocampus; locus coeruleus; memory.

Publication types

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

MeSH terms

  • Animals
  • Axons / physiology
  • Behavior, Animal
  • Dopamine / physiology*
  • Hippocampus / physiology*
  • Locus Coeruleus / physiology
  • Male
  • Memory*
  • Mice
  • Mice, Inbred C57BL
  • Neurons / physiology
  • Optogenetics
  • Spatial Learning*
  • Synaptic Transmission / physiology


  • Dopamine