R-type Ca2+ channels play a critical role in coupling excitability to dendritic Ca2+ influx and neuronal secretion. Unlike other types of voltage-sensitive Ca2+ channels (L, N, P/Q, and T type), the molecular basis for the R-type Ca2+ channel is still unclear, thereby limiting further detailed analyses of R-type Ca2+ channel physiology. The prevailing hypothesis is that α1E (CaV2.3) gene encodes for R-type Ca2+ channels, but the dearth of critical evidence has rendered this hypothesis controversial. Here we generated α1E-deficient mice (α1E−/−) and examined the status of voltage-sensitive Ca2+ currents in central amygdala (CeA) neurons that exhibit abundant α1E expression and R-type Ca2+ currents. The majority of R-type currents in CeA neurons were eliminated in α1E−/− mice whereas other Ca2+ channel types were unaffected. These data clearly indicate that the expression of α1E gene underlies R-type Ca2+ channels in CeA neurons. Furthermore, the α1E−/− mice exhibited signs of enhanced fear as evidenced by their vigorous escaping behavior and aversion to open-field conditions. These latter findings imply a possible role of α1E-based R-type Ca2+ currents in amygdala physiology associated with fear
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