Role of Thalamic Ca_V3.1 T-Channels in Fear Conditioning

The potential contribution of the ion channels that control the excitability of the midline and intralaminar nuclei of the thalamus to the modulation of behaviors has not been well studied. In this study, we used both global genetic deletion (knock-out, KO) and thalamus-specific molecular knock-down (KD) approaches to investigate the role of thalamic Ca_V3.1 T-type calcium channels (T-channels) in fear learning and fear responses. Previously, we have shown that the dominant subtype of T-channels in the central medial nucleus of the thalamus (CMT) is the Ca_V3.1 isoform and that CMT neurons from Ca_V3.1 KO animals have decreased burst firing. By specifically knocking down Ca_V3.1 T-channels in the CMT using the shRNA approach, we also reduced burst firing without affecting the tonic firing mode of the transfected neurons. We report that global Ca_V3.1 KO animals showed stronger freezing behaviors during both the conditioning and testing phases of contextual fear conditioning, while CMT-specific Ca_V3.1 KD mice only had stronger fear responses during testing. In contrast, the cue-mediated fear responses were similar between Ca_V3.1 KO and Ca_V3.1 KD mice and the controls. Our findings validate thalamic Ca_V3.1 T-channels as a potential new target for the development or treatment of different psychiatric diseases, such as post-traumatic stress disorder, schizophrenia, anxiety, and substance abuse disorders.