Mounting evidence shows that dopamine in the striatum is critically involved in reward-based reinforcement learning. However, it remains unclear how dopamine reward signals influence the entorhinal-hippocampal circuit, another brain network critical for learning and memory. Using in vivo optogenetic and electrophysiological approaches, we recently found that dopamine signals from the ventral tegmental area control encoding of cue-reward association rules in the lateral entorhinal cortex (LEC) (Lee et al., Nature, 2021). Our results suggest that LEC represent a cognitive map of abstract task rules, and LEC dopamine facilitates the incorporation of new memories into this map. I would like to discuss how we can unify the roles of two central, but previously independent, players in learning – dopamine and the entorhinal-hippocampal circuit – in future studies. In the second part of the talk, I will share our results on how neuronal activities in the entorhinal-hippocampal memory circuit are lost in a mouse model of Alzheimer’s disease (Jun et al., Neuron, 2020), and discuss how the systems neuroscience approach can contribute to the understanding of Alzheimer’s disease pathogenesis.

Reference:

Lee JY, Jun H, Soma S, Nakazono T, Shiraiwa K, Dasgupta A, Nakagawa T, Xie JL, Chavez J, Romo R, Yungblut Y, Hagihara M, Murata K, and Igarashi KM* (2021)
Dopamine facilitates associative memory encoding in the entorhinal cortex
Nature, 598:321-326

Jun H, Bramian A, Soma S, Saito T, Saido TC, Igarashi KM* (2020)
Disrupted Place Cell Remapping and Impaired Grid Cells in a Knockin Model of Alzheimer's Disease
Neuron, 107:1095-1112