1. Essential role for TRPC5 in amygdala function and fear-related behavior
- Author
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Evgeny Tsvetkov, Antonio Riccio, Svetlana Gapon, Kiersten S. Smith, Gui Lan Yao, Jisook Moon, Vadim Y. Bolshakov, Yan Li, Uwe Rudolph, Ashlee Van't Veer, Scott J. Rodig, Kwang-Soo Kim, David E. Clapham, Edward G. Meloni, and William A. Carlezon
- Subjects
Male ,Long-Term Potentiation ,Neurotransmission ,Biology ,Receptors, Metabotropic Glutamate ,Amygdala ,Synaptic Transmission ,General Biochemistry, Genetics and Molecular Biology ,MOLNEURO ,Article ,TRPC1 ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Conditioning, Psychological ,medicine ,Animals ,030304 developmental biology ,TRPC Cation Channels ,Mice, Knockout ,0303 health sciences ,Biochemistry, Genetics and Molecular Biology(all) ,Glutamate receptor ,Brain ,Long-term potentiation ,Fear ,Metabotropic receptor ,medicine.anatomical_structure ,Metabotropic glutamate receptor ,Excitatory postsynaptic potential ,Neuroscience ,030217 neurology & neurosurgery - Abstract
SUMMARY 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.
- Published
- 2008