Author/Authors :
Antonio Riccio، نويسنده , , Yan Li، نويسنده , , Jisook Moon، نويسنده , , Kwang-Soo Kim، نويسنده , , Kiersten S. Smith، نويسنده , , Uwe Rudolph، نويسنده , , Svetlana Gapon، نويسنده , , Gui Lan Yao، نويسنده , , Evgeny Tsvetkov، نويسنده , , Scott J. Rodig، نويسنده , , Ashlee Vanʹt Veer، نويسنده , , Edward G. Meloni، نويسنده , , William A. Carlezon Jr، نويسنده , , Vadim Y. Bolshakov، نويسنده , , David E. Clapham، نويسنده ,
Abstract :
The transient receptor potential channel 5 (TRPC5) is predominantly expressed in the brain where it can form heterotetrameric complexes with TRPC1 and TRPC4 channel subunits. These excitatory, nonselective cationic channels are regulated by G protein, phospholipase C-coupled receptors. Here, we show that TRPC5−/− mice exhibit diminished innate fear levels in response to innately aversive stimuli. Moreover, mutant mice exhibited significant reductions in responses mediated by synaptic activation of Group I metabotropic glutamate and cholecystokinin 2 receptors in neurons of the amygdala. Synaptic strength at afferent inputs to the amygdala was diminished in P10-P13 null mice. In contrast, baseline synaptic transmission, membrane excitability, and spike timing-dependent long-term potentiation at cortical and thalamic inputs to the amygdala were largely normal in older null mice. These experiments provide genetic evidence that TRPC5, activated via G protein-coupled neuronal receptors, has an essential function in innate fear.
