Schedule of Events | Symposia

The role of hyperpolarization-activated cation channel 1 in PTSD-like phenotypes induced by single prolonged stress with post-corticosterone treatment

Poster Session D - Monday, March 31, 2025, 8:00 – 10:00 am EDT, Back Bay Ballroom/Republic Ballroom

Chung Sub Kim¹ (ckim5@augusta.edu), Jiwon Kim¹; ¹Augusta University

Introduction Single Prolonged Stress (SPS) is an animal model frequently employed to investigate the physiological and behavioral effects of acute stress. Glucocorticoids can induce atypical fear memories, including contextual amnesia, characterized by the inability to recall specific events, and emotional hypermnesia, marked by excessive recollection of feelings associated with such events. Hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels are highly expressed in the dorsal CA1 region of the hippocampus, where they modulate both intrinsic and synaptic neuronal properties. The role of HCN1 channels in maladaptive fear memories is not well understood. Methods 8–to-9-week-old male mice underwent SPS followed by post-treatment with vehicle or corticosterone (CORT). Y-maze and contextual fear conditioning were conducted. Following behavioral tests, whole-cell current- and voltage-clamp recordings were performed in the dorsal CA1 neurons. HCN1 overexpression in dorsal CA1 neurons was achieved through pLenti-CaMKIIα-HCN1 injections. Results SPS-CORT-treated mice displayed decreased spatial working memory, contextual amnesia, and impaired fear extinction compared to control-vehicle or -CORT groups. Dorsal CA1 neurons from SPS-CORT-treated mice displayed decreased input resistance (Rin) and reduced action potential (AP) firing compared to control-CORT group. Hyperpolarization-activated current (Ih) was significantly increased. ZD7288, HCN channels blocker, reversed the observed changes in Rin, AP firing, and Ih. Mice with HCN1 gene overexpression exhibited the phenotype seen in SPS-CORT-treated mice. Conclusion Our findings suggest that SPS with post-CORT treatment induces PTSD-like symptoms, which were reproduced by overexpression of HCN1 gene in dorsal CA1 neurons, highlighting the role of HCN1 channels as potential contributors to PTSD-like phenotypes.

Topic Area: EMOTION & SOCIAL: Emotion-cognition interactions