title: Essential role for TRPC5 in amygdala function and fear-related behavior.
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.
authors.affiliation: Department of Cardiology, Howard Hughes Medical Institute, Manton Center for Orphan Disease, Children's Hospital Boston, Boston, MA 02115, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Riccio
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Jisook
authors.initials: J
authors.lastname: Moon
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Kim
authors.forename: Kiersten S
authors.initials: KS
authors.lastname: Smith
authors.forename: Uwe
authors.initials: U
authors.lastname: Rudolph
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gapon
authors.forename: Gui Lan
authors.initials: GL
authors.lastname: Yao
authors.forename: Evgeny
authors.initials: E
authors.lastname: Tsvetkov
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Rodig
authors.forename: Ashlee
authors.initials: A
authors.lastname: Van't Veer
authors.forename: Edward G
authors.initials: EG
authors.lastname: Meloni
authors.forename: William A
authors.initials: WA
authors.lastname: Carlezon
authors.forename: Vadim Y
authors.initials: VY
authors.lastname: Bolshakov
authors.forename: David E
authors.initials: DE
authors.lastname: Clapham
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001921:Brain; D003213:Conditioning, Psychological; D005239:Fear; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D009435:Synaptic Transmission; D050052:TRPC Cation Channels / Q000235:genetics / Q000502:physiology*
chemical_list: D018094:Receptors, Metabotropic Glutamate; D050052:TRPC Cation Channels; C112021:Trpc5 protein, mouse