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Proc Natl Acad Sci U S A ; 118(40)2021 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-34580198

RESUMEN

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.


Asunto(s)
Dopamina/metabolismo , Hipocampo/metabolismo , Memoria/fisiología , Animales , Neuronas Dopaminérgicas , Miedo/fisiología , Femenino , Aprendizaje/fisiología , Masculino , Mesencéfalo/fisiología , Ratones , Ratones Endogámicos C57BL , Optogenética/métodos , Sustancia Negra/metabolismo , Área Tegmental Ventral/fisiología
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