Essential role for TRPC5 in amygdala function and fear-related behavior

Cell. 2009 May 15;137(4):761-72. doi: 10.1016/j.cell.2009.03.039.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / physiology*
  • Animals
  • Brain
  • Conditioning, Psychological
  • Fear*
  • Long-Term Potentiation
  • Male
  • Mice
  • Mice, Knockout
  • Receptors, Metabotropic Glutamate / physiology
  • Synaptic Transmission
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / physiology*


  • Receptors, Metabotropic Glutamate
  • TRPC Cation Channels
  • Trpc5 protein, mouse