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Updated: Jun 11, 2025

Aversive Associative Learning and Memory Formation by Pairing Two Chemicals in Caenorhabditis elegans
Published on: June 23, 2022
HCN channel-dependent presynaptic potentiation at LA-BA synapses is required for fear memory formation
Kyuhyun Choi1, Jee Hyun Yi1, Kyungjoon Park1
1Department of Biology, Kyung Hee University, Seoul, 02447, Republic of Korea.
Abstract:
Previously, we demonstrated that auditory fear conditioning produces presynaptic potentiation at lateral to basal amygdala (LA-BA) synapses, which occludes high-frequency stimulation (HFS)-induced ex-vivo LTP. We also found that the HFS-induced ex-vivo LTP requires presynaptic hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity. In this study, we investigated whether HCN channels are necessary for auditory fear conditioning in vivo. Our results show that ZD7288, an HCN channel blocker, reduced synaptic transmission and decreased the paired pulse ratio (PPR) only in slices from rats that underwent auditory fear conditioning, but not from naïve rats. This indicates that fear conditioning involves HCN channel-dependent presynaptic potentiation at LA-BA synapses. Importantly, injecting ZD7288 into the basal amygdala (BA) before auditory fear conditioning significantly impaired long-term fear memory formation. Since HCN channel activity is necessary for LTP at LA-BA synapses but not at cortico-BA, cortico-LA, or thalamo-LA synapses, HCN channel-dependent presynaptic potentiation at LA-BA synapses appears to be crucial for auditory fear conditioning.
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