Essential Role for TRPC5 in Amygdala Function and Fear-Related Behavior

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, non-selective 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.

Oxytocin Stimulates Extracellular Ca2+ Influx Through TRPV2 Channels in Hypothalamic Neurons to Exert Its Anxiolytic Effects

“…Two other TRP channels have been described to be involved in the control of anxiety and fear, namely TRPC5 and TRPV1. In contrast to the anxiolytic effect of TRPV2 in the PVN, however, TRPC5 seems to be anxiogenic in the amygdala, as TRPC5 −/− mice exhibit diminished innate fear in tests for general and social anxiety (Riccio et al, 2009). Likewise, TRPV1 knockout mice show decreased anxiety-like behavior in the LDB and EPM, as well as reduced conditioned fear, suggesting that TRPV1 activity promotes anxiogenic behavior (Marsch et al, 2007).…”

TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells

“…TRPV1 is a heat-responsive ion channel, TRPM8 senses cold, and TRPM2 is sensitive to oxidative stress (Wu et al, 2010) and is fundamental in signalling cascades responsible for acetaminophen ( paracetamol)-induced liver damage (Kheradpezhouh et al, 2014). TRPC5 is important in semaphorin 3A-induced neuronal growth cone collapse (Kaczmarek et al, 2012) and fear-related behaviour (Riccio et al, 2009), and is also associated with the acquisition of multidrug resistance in breast cancer cells (Ma et al, 2012. TRPC1 was the first TRP ion channel identified in mammals (Wu et al, 2010) and it is expressed in a variety of cell types (Cheng et al, 2013;Nilius and Szallasi, 2014); however, a detailed understanding of its role(s) in many contexts remains unclear and controversial.…”

Assessing the Kinesiophobia and Depression Status at Return to Sport Following Sport Related Injuries in Contact and Non-Contact Sports

“…Korku, acı ya da ağrı tehdidi gibi daha önceden deneyimlenen durumlara tepki olarak kaçma ve kaçınma özellikli davranışları tetikleyebilir. Kinezyofobi olarak isimlendirilen yeniden yaralanma korkusu, limbik sistem yapılarından amigdala ve insula bölgeleri ile bağlantılı bir korku çeşididir (8,9). …”