Journal
NATIONAL SCIENCE REVIEW
Volume 8, Issue 9, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nsr/nwab004
Keywords
fear renewal; memory ensembles; input associativity; long-term potentiation; ventral hippocampus; auditory cortex; lateral amygdala
Categories
Funding
- National Natural Science Foundation of China [31930050, 81771214, 31900701, 32071023, 81903583]
- Science and Technology Commission of Shanghai Municipality [18JC1420302, 18QA1402500]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX05]
- SJTU Transmed Awards Research [2019015]
- innovative research team of high-level local universities in Shanghai
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Research shows that fear renewal is determined by the associativity between convergent inputs from the auditory cortex and ventral hippocampus onto the lateral amygdala, reactivating ensembles engaged during learning. Fear renewal enhances synaptic strengths of both inputs and optogenetic activation of their input associativity in the LA recapitulates fear renewal. Input associativity underlies fear memory renewal.
Synaptic associativity, a feature of Hebbian plasticity wherein coactivation of two inputs onto the same neuron produces synergistic actions on postsynaptic activity, is a primary cellular correlate of associative learning. However, whether and how synaptic associativity are implemented into context-dependent relapse of extinguished memory (i.e. fear renewal) is unknown. Here, using an auditory fear conditioning paradigm in mice, we show that fear renewal is determined by the associativity between convergent inputs from the auditory cortex (ACx) and ventral hippocampus (vHPC) onto the lateral amygdala (LA) that reactivate ensembles engaged during learning. Fear renewal enhances synaptic strengths of both ACx to LA and the previously unknown vHPC to LA monosynaptic inputs. While inactivating either of the afferents abolishes fear renewal, optogenetic activation of their input associativity in the LA recapitulates fear renewal. Thus, input associativity underlies fear memory renewal.
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