Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 40, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2111069118
Keywords
fear conditioning; optogenetics; ventral tegmental area; locus coeruleus; substantia nigra pars compacta
Categories
Funding
- NIH [NS021229, AA026267, MH080333]
- NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development U54 Grant [HD086984]
- Chernowitz Medical Research Foundation
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This study identifies a cluster of midbrain dopamine neurons near the hippocampus that send direct projections and play a crucial role in aversive memory formation. The neuromodulation of midbrain dopamine in the hippocampus is sufficient to maintain aversive memory formation.
Aversive memories are important for survival, and dopaminergic signaling in the hippocampus has been implicated in aversive learning. However, the source and mode of action of hippocampal dopamine remain controversial. Here, we utilize anterograde and retrograde viral tracing methods to label midbrain dopaminergic projections to the dorsal hippocampus. We identify a population of midbrain dopaminergic neurons near the border of the substantia nigra pars compacta and the lateral ventral tegmental area that sends direct projections to the dorsal hippocampus. Using optogenetic manipulations and mutant mice to control dopamine transmission in the hippocampus, we show that midbrain dopamine potently modulates aversive memory formation during encoding of contextual fear. Moreover, we demonstrate that dopaminergic transmission in the dorsal CA1 is required for the acquisition of contextual fear memories, and that this acquisition is sustained in the absence of catecholamine release from noradrenergic terminals. Our findings identify a cluster of midbrain dopamine neurons that innervate the hippocampus and show that the midbrain dopamine neuromodulation in the dorsal hippocampus is sufficient to maintain aversive memory formation.
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