Dopamine facilitates associative memory encoding in the entorhinal cortex

Jason Y. Lee, Heechul Jun, Shogo Soma, Tomoaki Nakazono, Kaori Shiraiwa, Ananya Dasgupta, Tatsuki Nakagawa, Jiayun L. Xie, Jasmine Chavez, Rodrigo Romo, Sandra Yungblut, Meiko Hagihara, Koshi Murata and Kei M. Igarashi ()
Additional contact information
Jason Y. Lee: University of California, Irvine
Heechul Jun: University of California, Irvine
Shogo Soma: University of California, Irvine
Tomoaki Nakazono: University of California, Irvine
Kaori Shiraiwa: University of California, Irvine
Ananya Dasgupta: University of California, Irvine
Tatsuki Nakagawa: University of California, Irvine
Jiayun L. Xie: University of California, Irvine
Jasmine Chavez: University of California, Irvine
Rodrigo Romo: University of California, Irvine
Sandra Yungblut: University of California, Irvine
Meiko Hagihara: University of Fukui
Koshi Murata: University of Fukui
Kei M. Igarashi: University of California, Irvine

Nature, 2021, vol. 598, issue 7880, 321-326

Abstract: Abstract Mounting evidence shows that dopamine in the striatum is critically involved in reward-based reinforcement learning1,2. However, it remains unclear how dopamine reward signals influence the entorhinal–hippocampal circuit, another brain network that is crucial for learning and memory3–5. Here, using cell-type-specific electrophysiological recording6, we show that dopamine signals from the ventral tegmental area and substantia nigra control the encoding of cue–reward association rules in layer 2a fan cells of the lateral entorhinal cortex (LEC). When mice learned novel olfactory cue–reward associations using a pre-learned association rule, spike representations of LEC fan cells grouped newly learned rewarded cues with a pre-learned rewarded cue, but separated them from a pre-learned unrewarded cue. Optogenetic inhibition of fan cells impaired the learning of new associations while sparing the retrieval of pre-learned memory. Using fibre photometry, we found that dopamine sends novelty-induced reward expectation signals to the LEC. Inhibition of LEC dopamine signals disrupted the associative encoding of fan cells and impaired learning performance. These results suggest that LEC fan cells represent a cognitive map of abstract task rules, and that LEC dopamine facilitates the incorporation of new memories into this map.

Date: 2021
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DOI: 10.1038/s41586-021-03948-8

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