Ventral tegmental area dopamine projections to the hippocampus trigger long-term potentiation and contextual learning

Fares J. P. Sayegh (), Lionel Mouledous, Catherine Macri, Juliana Pi Macedo, Camille Lejards, Claire Rampon, Laure Verret and Lionel Dahan ()
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Fares J. P. Sayegh: Université de Toulouse; CNRS, UPS
Lionel Mouledous: Université de Toulouse; CNRS, UPS
Catherine Macri: Université de Toulouse; CNRS, UPS
Juliana Pi Macedo: Université de Toulouse; CNRS, UPS
Camille Lejards: Université de Toulouse; CNRS, UPS
Claire Rampon: Université de Toulouse; CNRS, UPS
Laure Verret: Université de Toulouse; CNRS, UPS
Lionel Dahan: Université de Toulouse; CNRS, UPS

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract In most models of neuronal plasticity and memory, dopamine is thought to promote the long-term maintenance of Long-Term Potentiation (LTP) underlying memory processes, but not the initiation of plasticity or new information storage. Here, we used optogenetic manipulation of midbrain dopamine neurons in male DAT::Cre mice, and discovered that stimulating the Schaffer collaterals – the glutamatergic axons connecting CA3 and CA1 regions - of the dorsal hippocampus concomitantly with midbrain dopamine terminals within a 200 millisecond time-window triggers LTP at glutamatergic synapses. Moreover, we showed that the stimulation of this dopaminergic pathway facilitates contextual learning in awake behaving mice, while its inhibition hinders it. Thus, activation of midbrain dopamine can operate as a teaching signal that triggers NeoHebbian LTP and promotes supervised learning.

Date: 2024
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DOI: 10.1038/s41467-024-47481-4

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