Essential role for TRPC5 in amygdala function and fear-related behavior.
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.
Riccio
Antonio
A
Department of Cardiology, Howard Hughes Medical Institute, Manton Center for Orphan Disease, Children's Hospital Boston, Boston, MA 02115, USA.
Li
Yan
Y
Moon
Jisook
J
Kim
Kwang-Soo
KS
Smith
Kiersten S
KS
Rudolph
Uwe
U
Gapon
Svetlana
S
Yao
Gui Lan
GL
Tsvetkov
Evgeny
E
Rodig
Scott J
SJ
Van't Veer
Ashlee
A
Meloni
Edward G
EG
Carlezon
William A
WA
Bolshakov
Vadim Y
VY
Clapham
David E
DE
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*
D018094:Receptors, Metabotropic Glutamate; D050052:TRPC Cation Channels; C112021:Trpc5 protein, mouse