Heterosynaptic plasticity of the visuo-auditory projection requires cholecystokinin released from entorhinal cortex afferents
- City University of Hong Kong, Hong Kong
- Karolinska Institute, Sweden
- City University of Hong Kong, China
Abstract
The entorhinal cortex is involved in establishing enduring visuo-auditory associative memory in the neocortex. Here we explored the mechanisms underlying this synaptic plasticity related to projections from the visual and entorhinal cortices to the auditory cortex in mice, using optogenetics of dual pathways. High-frequency laser stimulation (HFS laser) of the visuo-auditory projection did not induce long-term potentiation (LTP). However, after pairing with sound stimulus, the visuo-auditory inputs were potentiated following either infusion of cholecystokinin (CCK) or HFS laser of the entorhino-auditory CCK-expressing projection. Combining retrograde tracing and RNAscope in situ hybridization, we show that Cck expression is higher in entorhinal cortex neurons projecting to the auditory cortex than in those originating from the visual cortex. In the presence of CCK, potentiation in the neocortex occurred when the presynaptic input arrived 200 ms before postsynaptic firing, even after just five trials of pairing. Behaviorally, inactivation of the CCK+ projection from the entorhinal cortex to the auditory cortex blocked the formation of visuo-auditory associative memory. Our results indicate that neocortical visuo-auditory association is formed through heterosynaptic plasticity, which depends on release of CCK in the neocortex mostly from entorhinal afferents.
Data availability
Source Data files have been provided for figures 1 to 6 and supplementary figures.
Article and author information
Author details
Funding
Hong Kong Research Grants Council (General Research Fund,11103220M)
- Jufang He
The Swedish Research Council (220-01688)
- Tomas Hökfelt
Key-Area Research and Development Program of Guangdong Province (2018B030340001)
- Wenjian Sun
Wong Chun Hong Endowed Chair Professorship
- Jufang He
Charlie Lee Charitable Foundation
- Jufang He
Fong Shu Fook Tong Foundation
- Jufang He
Hong Kong Research Grants Council (General Research Fund,11101521M)
- Jufang He
Hong Kong Research Grants Council (Collaborative Research Fund,C1043-21GF)
- Jufang He
Hong Kong Innovation and Technology Commission (Innovation and Technology Fund,MRP/053/18X)
- Jufang He
Hong Kong Innovation and Technology Commission (Innovation and Technology Fund,GHP_075_19GD)
- Jufang He
Hong Kong health bureau (Health and Medical Research Fund,06172456)
- Xi Chen
Hong Kong health bureau (Health and Medical Research Fund,09203656)
- Jufang He
The Swedish Research Council (2018-0273)
- Tomas Hökfelt
The Arvid Carlsson Foundation
- Tomas Hökfelt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental procedures were approved by the Animal Subjects Ethics Sub-Committees of City University of Hong Kong (Reference number of animal ethics review: A-59 and A-0467).
Copyright
© 2024, Sun et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Heterosynaptic plasticity of the visuo-auditory projection requires cholecystokinin released from entorhinal cortex afferents
eLife 13:e83356.
https://doi.org/10.7554/eLife.83356
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