Department of Biology, Kyung Hee University, Seoul, 02447, Republic of Korea.
Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, 05006, Republic of Korea.
Biochem Biophys Res Commun. 2024 Nov 19;734:150788. doi: 10.1016/j.bbrc.2024.150788. Epub 2024 Oct 2.
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.
先前，我们证明了听觉恐惧条件反射会在外侧杏仁核-基底杏仁核（LA-BA）突触产生突触前易化，从而阻断高频刺激（HFS）诱导的离体长时程增强（LTP）。我们还发现，HFS 诱导的离体 LTP 需要突触前超极化激活环核苷酸门控（HCN）通道活性。在这项研究中，我们研究了 HCN 通道是否是体内听觉恐惧条件反射所必需的。我们的结果表明，HCN 通道阻断剂 ZD7288 仅在接受过听觉恐惧条件反射的大鼠的切片中减少了突触传递并降低了成对脉冲比（PPR），而在未接受过训练的大鼠的切片中则没有。这表明恐惧条件反射涉及 LA-BA 突触的 HCN 通道依赖性突触前易化。重要的是，在听觉恐惧条件反射之前将 ZD7288 注射到基底杏仁核（BA）中，显著损害了长期恐惧记忆的形成。由于 HCN 通道活性对于 LA-BA 突触处的 LTP 是必需的，但对于皮质-基底杏仁核、皮质-外侧杏仁核或丘脑-外侧杏仁核突触处的 LTP 则不是必需的，因此 LA-BA 突触处的 HCN 通道依赖性突触前易化似乎对听觉恐惧条件反射至关重要。
