GELIFES Seminars - Ron Stoop

Ron Stoop (Universite of Lausanne)

Active coping with fear - A pathway in the amygdala sensitive to oxytocin

Effective coping with fear can be an important strategy to avoid the development of anxiety and fear disorders. When facing a threat, humans and animals can respond passively by freezing or actively by avoiding/escaping the threat. Over the last decades, the freezing response in rodents has been intensively studied as a model for a direct readout of fear. When giving a population of rats the possibility to avoid an imminent threat, however, some may rapidly escape while others remain dead frozen. The neuronal pathways underlying this divergence remain still unclear.

Fear is known to activate the amygdala, the fear center of the brain. The central nucleus of the amygdala sends projections to the brain stem that underlie the physiological expression of fear, of which the projections to the periaqueductal grey trigger freezing. In the past, we have shown that oxytocin can activate a local, inhibitory pathway within the central amygdala (Huber et al., 2005) and that this pathway can specifically inhibit projections to the periaqueductal grey (Viviani et al., 2011). This opened up the question whether differences in oxytocin signaling might affect the freezing versus escape response. To address this question, we started out from an observation in a unique population of humans who suffer from Urbach Wiethe disease which results in a selective calcification of the basolateral amygdala, leaving the central amygdala intact. These patients exhibited increased freezing and decreased escape when facing an imminent threat. By modeling this damage in rats we discovered how projections from the basolateral amygdala to oxytocin-responsive neurons in the central amygdala can inhibit freezing and promote escape to imminent threat. In my talk I will show how inherent differences in oxytocin signaling, related with social interactions and dominance patterns, can prime rats to develop escape or freezing responses. Social interactions, and concomitant signaling of oxytocin, may thus affect our strategies to cope with imminent threats.

Huber D, Veinante P, Stoop R. Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala Science. 2005 Apr 8;308(5719):245-8.

Viviani D, Charlet A, van den Burg E, Robinet C, Hurni N, Abatis M, Magara F, Stoop R. Oxytocin selectively gates fear responses through distinct outputs from the central amygdala. Science. 2011 Jul 1;333(6038):104-7.

Terburg D, Scheggia D, Triana Del Rio R, Klumpers F, Ciobanu AC, Morgan B, Montoya ER, Bos PA, Giobellina G, van den Burg EH, de Gelder B, Stein DJ, Stoop R*, van Honk J. The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study. Cell. 2018 Oct 18;175(3):723-735