CACNA1C is associated with auditory related fear enhancement in single prolonged stress male rats.

Abstract

BACKGROUND: CACNA1C, a gene that encodes Cav 1.2 an alpha-1 subunit of L-type voltage-gated calcium channels (LTCC), has been associated with post-traumatic stress disorder (PTSD). Enhanced fear memory is a typical symptom of PTSD. The aim of the present experiment was to explore the role of calcium channels and related genes on auditory related fear in PTSD. METHOD: We employed single prolonged stress (SPS) as the animal model of PTSD in male rats. Multiple start sound amplitudes at 95 dB, 105 dB and 115 dB of Acoustic startle response (ASR) and inhibitory gating (IG) recording were used to assess behavioral changes. We used Whole-cell patch clamp technique to evaluate the function of LTCC. The immunofluorescence staining, Western Blotting and qPCR were used to test the protein and mRNA expression in signal transduction pathways. RESULTS: The data showed that the percentage amplitude of the startle response increased at 115 dB and the ratio of testing tone (T)/conditioning tone (C) increased at negative deflection of local field potential (LFP) at about 25 ms (N25) after exposure to SPS. The Cacurrents density was decreased in SPS rats. The protein and mRNA expression of CACNA1C showed significant up regulation in SPS rats. The results also indicated abnormalities in the mitogen-activated protein kinase (MAPK) signal pathway. CONCLUSION: These data demonstrated that CACNA1C is associated with auditory related fear enhancement after exposure to SPS. We speculate that enhanced fear memory may be regulated through CACNA1C and calcium channel signal transduction pathways.