Midbrain dopaminergic innervation of the hippocampus is sufficient to modulate formation of aversive memories.

Autor:	Tsetsenis T; Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104; theot@pennmedicine.upenn.edu johndani@pennmedicine.upenn.edu., Badyna JK; Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104., Wilson JA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104., Zhang X; Department of Systems Pharmacology and Translational Therapeutics, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104., Krizman EN; Department of Systems Pharmacology and Translational Therapeutics, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104.; Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104., Subramaniyan M; Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104., Yang K; Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104., Thomas SA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104., Dani JA; Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104; theot@pennmedicine.upenn.edu johndani@pennmedicine.upenn.edu.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Oct 05; Vol. 118 (40).
DOI:	10.1073/pnas.2111069118
Abstrakt:	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. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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